Clusterin基因在奶牛乳腺炎中的作用及表达调控机制
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摘要
奶牛乳腺炎是乳腺组织受到物理,化学,微生物等刺激引发乳腺病变,对奶牛养殖业造成巨大损失。对奶牛乳腺炎发病机理和防治技术的研究已有一个多世纪,大多是从乳腺炎表型症状出发,探寻一些合理的管理技术和防治手段,虽然取得一些疗效,但仍未能从根本上解决奶牛乳腺炎的发生和彻底的控制。本研究拟从基因遗传角度出发,探寻奶牛抗乳腺炎的新方法,试图找到与奶牛乳腺炎抗性相关的基因,研究和分析某基因在奶牛乳腺炎发病中的作用及表达调控的分子机制。
1Clusterin基因SNP检测及其与奶牛乳腺炎的相关性分析
本研究测序发现在CLU基因的5’调控区,编码区,3’非翻译区都存在SNP,通过分析不同SNP与1000多头中国荷斯坦牛产奶量,乳脂率,乳蛋白率,体细胞数评分,脂蛋比,总奶量,总乳脂,总乳蛋白等产奶性能的相关性,从多态效应,基因替换效应,单倍型组合效益,胎次效应来分析和探讨CLU基因与乳腺炎的相关性。根据实验研究发现,CLU基因在中国荷斯坦牛群体内的遗传变异较低,处于中度多态,突变产生正效应占优势,产奶性能优良的单倍型组合H1H4在牛群中数量不占优势,胎次效应为正,但产奶性能提高的同时伴随体细胞评分的上升,尤其是第四胎牛,产奶性能上升速率趋于平缓,但体细胞评分却偏高。+17301T突变可作为抗奶牛乳腺炎的遗传标记辅助选择指标。
2Clusterin基因乳腺特异启动子构建及功能验证
本研究克隆获得不同长度片段的CLU基因5’调控区序列,生物信息分析不同片段都含有启动子特有的TATAbox,转录因子结合位点和CpG岛。将不同长度片段的CLU基因5’调控区序列分别导入PGL3-Basic荧光素酶表达载体后转染293T细胞发现,CLU基因5’调控区的F1启动子活性很弱,且C-994T突变对F1启动子影响不明显,F2启动子具有很强的启动子活性。然后利用F2启动子高活性的特点,分别构建了包含不同启动子的CLU基因表达载体pEGFP-N1-CMV-CLU, pEGFP-Nl-F2-CLU和pEGFP-N1-CMV-F2-CLU,转染293T细胞和乳腺上皮细胞后发现pEGFP-N1-F2-CLU和pEGFP-N1-CMV-F2-CLU都可以激发CLU基因的表达,并且在293T细胞中的活性要高。而复合启动子表达载体pEGFP-N1-CMV-F2-CLU在293T细胞和乳腺上皮细胞中激活CLU基因表达的能力最强,且明显观察到CLU基因在细胞质中表达。
3奶牛乳腺组织中Clusterin基因的可变剪切体鉴定及表达
本研究乳腺炎致病菌分离鉴定为金黄色葡萄球菌,克隆测序发现在乳腺炎乳腺组织中发生内部外显子剪切,实行可变剪切模式,形成两种亚型X-CLU和Y-CLU。编码区SNP导致高频剪切位点消失和CLU基因mRNA二级结构发生剧烈变化。CLU基因乳腺组织体内表达显示,X-CLU和Y-CLU在正常乳腺组织和乳腺炎乳腺组织中的表达量差异显著,X-CLU在乳腺炎乳腺组织中mRNA表达量上调。在6个正常乳腺组织和6个乳腺炎乳腺组织中都出现了80kDa的蛋白条带,但是在第二个正常乳腺组织和第一个乳腺炎乳腺组织中出现了60kDa的蛋白条带。构建的CLU基因复合启动子表达载体pEGFP-N1-CMV-F2-X-CLU和pEGFP-N1-CMV-F2-Y-CLU分别转染乳腺上皮细胞进行乳腺组织体外表达显示只检测到X-CLU的mRNA表达,且蛋白分子量约60kDa,而Y-CLU没有表达。80kDa的蛋白可能是机体适应某种环境伴随X-CLU和Y-CLU两种蛋白的相互作用而形成的蛋白复合体。
4Clusterin基因3’UTR靶标确证奶牛乳腺炎抗性相关microRNA
本研究在CLU基因3’UTR区发现3个突变位点,生物信息分析发现+17301T缺失突变对miRNA的结合情况起关键作用。生产性能相关性研究显示+17301T突变与乳腺炎成正相关。CLU基因3’UTR在+17301T突变前结合bta-miR-2373,但T缺失后不结合。本研究中心基因芯片结果显示在中国荷斯坦牛乳腺炎乳腺组织中bta-miR-2373表达下调4.0倍。因此选择bta-miR-2373作为乳腺炎相关miRNA进行研究,实验证明,miRNA前体表达克隆载体CCS-bta2373-MR04在293T细胞中过表达,与CLU基因3’UTR靶标表达克隆载体pMIR-REPORT-miRNA-PT共转后,两者几乎完全结合,从而抑制CLU基因表达,CCS-bta2373-MR04也可以部分结合pMIR-REPORT-miRNA-PT-SNP降低CLU基因表达。因此,在乳腺炎发病过程中,降低内源性bta-miR-2373的表达,可上调CLU基因表达量,增强奶牛乳腺炎抗性。所以说,bta-miR-2373参与奶牛乳腺炎的发生和发展,可作为奶牛乳腺炎抗病育种的选择指标。
Bovine mastitis is a breast lesion caused by physical, chemical, or microbial stimulation. In cows, it can cause huge losses in milk production and is therefore of great importance in dairy farming. Although the symptoms and methods for prevention of mastitis in dairy cows have been studied for nearly a century with some effect, its pathogenic mechanisms are still largely unknown and thus the problem cannot be completely controlled. Here, we analyzed the role of clusterin as a potential mastitis resistance gene. We investigated the molecular mechanisms of clusterin gene regulation and its role in mastitis and milk production traits.
1Detection of single nucleotide polymorphisms (SNPs) in the bovine clusterin gene and their association with mastitis and milk production traits
In this study, we analyzed the association of the clusterin (CLU) gene with bovine mastitis and milk traits. By sequencing, we detected SNPs in the5'flanking region, coding region, and3'untranslated region (UTR) of the CLU gene. We then analyzed the identified polymorphisms and their haplotypes, as well as birth order, for association with mastitis and the milk production traits of more than1000Chinese Holstein cows. The milk production traits analyzed were:milk yield, milk fat, milk protein percentage, somatic cell count, lipoprotein ratio, total milk volume, total milk fat, total milk protein, and milk performance. We found that, although there is little genetic variation among Chinese Holstein cows, a+17301T deletion in the CLU gene3'UTR was associated with mastitis and could therefore be used as a marker. The previously reported haplotype HH4was not associated with any trait. The birth order effect was important:somatic cell count increased with more previous births and milk performance stopped improving after the fourth birth.
2In silico and functional analysis of the clusterin promoter
Next, we analyzed the5'flanking region of the bovine CLU gene by bioinformatics. We then cloned different fragments containing promoter (TATA box) fragments, transcription factor binding sites, and/or CpG islands into the pGL3-Basic luciferase expression vector. We then analyzed promoter activity after transfection into293T cells. We found that the F1promoter had very weak activity, and that the C994T polymorphism within it had no notable effect. However, the F2promoter had strong activity. We then generated enhanced green fluorescent protein (EGFP)-based expression vectors with different F2-related promoters (pEGFP-N1-CMV-CLU, pEGFP-N1-F2-CLU, and pEGFP-N1-CMV-F2-CLU) and transfected them into293T cells and mammary epithelial cells. We found that both the pEGFP-N1-F2-CLU and pEGFP-N1-CMV-F2-CLU constructs could stimulate high levels of CLU gene expression and activity in293T cells. Expression of the composite promoter vector, pEGFP-N1-CMV-F2-CLU, activated CLU gene expression the strongest, and we observed expressed CLU protein in the cytoplasm.
3Alternative splicing and expression of the clusterin gene in healthy and mastitis-infected mammary tissue in Chinese Holstein cows
We cloned and sequenced the CLU mRNAs identified in mastitis-affected mammary tissue to examine alternative splicing. We identified two alternative splice variants, X-CLU and Y-CLU. Moreover, a SNP in the coding region led to the loss of many shear sites and caused dramatic changes in the CLU mRNA secondary structure. Both the X-CLU and Y-CLU alternative splice variants were expressed in vivo in normal and mastitis-affected breast tissue, but the expression of X-CLU was increased significantly in mastitis. At the protein level, an80-kDa CLU band was present in normal and mastitis-affected breast tissue (n=6each) and a60-kDa band was observed in one sample of each. When we generated constructs specifically expressing either splice form (pEGFP-N1-CMV-F2-X-CLU and pEGFP-N1-CMV-F2-Y-CLU) and expressed them in mammary epithelial cells, we could detect expression of the X-CLU mRNA and the60-kDa protein, but not the Y-CLU mRNA or the80-kDa band. The Y-CLU-derived,80-kDa protein may be expressed only in certain environmental conditions, and may form protein complexes with the X-CLU-derived60-kDa protein.
4A clusterin SNP affecting microRNA binding is associated with mastitis in dairy cattle
Of the three variants we identified the3'UTR of the CLU gene, bioinformatics analysis of the mastitis-associated+17301T deletion suggested that this site may play an important role in microRNA (miRNA) binding. We found that the normal allele bound to bta-miR-2373, but that this binding was abolished in the presence of the+17301T deletion. Moreover, we demonstrated by gene-chip analysis that bta-miR-2373was downregulated four-fold in mastitis-affected breast tissue from Chinese Holstein cattle compared with in non-affected tissue. Study found that MicroRNA precursor expression cloning vector CCS-bta2373-MR04in293T cells overexpress, CLU gene3'UTR of target expression cloning vector pMIR-REPORT-miRNA-PT is almost can be fully combined with CCS-bta2373-MR04completely inhibit the bta-miR-2373expression, pMIR-REPORT-miRNA-PT-SNP can also be part of the combination CCS-bta2373-MR04and reduce the bta-miR-2373expression, resulting in mastitis pathogenesis in the up-regulation of CLU gene expression, participation in mastitis occurrence and development. We propose that the expression level of bta-miR-2373can be used as a mastitis resistance breeding selection marker in dairy cows.
1Clusterin基因SNP检测及其与奶牛乳腺炎的相关性分析
本研究测序发现在CLU基因的5’调控区,编码区,3’非翻译区都存在SNP,通过分析不同SNP与1000多头中国荷斯坦牛产奶量,乳脂率,乳蛋白率,体细胞数评分,脂蛋比,总奶量,总乳脂,总乳蛋白等产奶性能的相关性,从多态效应,基因替换效应,单倍型组合效益,胎次效应来分析和探讨CLU基因与乳腺炎的相关性。根据实验研究发现,CLU基因在中国荷斯坦牛群体内的遗传变异较低,处于中度多态,突变产生正效应占优势,产奶性能优良的单倍型组合H1H4在牛群中数量不占优势,胎次效应为正,但产奶性能提高的同时伴随体细胞评分的上升,尤其是第四胎牛,产奶性能上升速率趋于平缓,但体细胞评分却偏高。+17301T突变可作为抗奶牛乳腺炎的遗传标记辅助选择指标。
2Clusterin基因乳腺特异启动子构建及功能验证
本研究克隆获得不同长度片段的CLU基因5’调控区序列,生物信息分析不同片段都含有启动子特有的TATAbox,转录因子结合位点和CpG岛。将不同长度片段的CLU基因5’调控区序列分别导入PGL3-Basic荧光素酶表达载体后转染293T细胞发现,CLU基因5’调控区的F1启动子活性很弱,且C-994T突变对F1启动子影响不明显,F2启动子具有很强的启动子活性。然后利用F2启动子高活性的特点,分别构建了包含不同启动子的CLU基因表达载体pEGFP-N1-CMV-CLU, pEGFP-Nl-F2-CLU和pEGFP-N1-CMV-F2-CLU,转染293T细胞和乳腺上皮细胞后发现pEGFP-N1-F2-CLU和pEGFP-N1-CMV-F2-CLU都可以激发CLU基因的表达,并且在293T细胞中的活性要高。而复合启动子表达载体pEGFP-N1-CMV-F2-CLU在293T细胞和乳腺上皮细胞中激活CLU基因表达的能力最强,且明显观察到CLU基因在细胞质中表达。
3奶牛乳腺组织中Clusterin基因的可变剪切体鉴定及表达
本研究乳腺炎致病菌分离鉴定为金黄色葡萄球菌,克隆测序发现在乳腺炎乳腺组织中发生内部外显子剪切,实行可变剪切模式,形成两种亚型X-CLU和Y-CLU。编码区SNP导致高频剪切位点消失和CLU基因mRNA二级结构发生剧烈变化。CLU基因乳腺组织体内表达显示,X-CLU和Y-CLU在正常乳腺组织和乳腺炎乳腺组织中的表达量差异显著,X-CLU在乳腺炎乳腺组织中mRNA表达量上调。在6个正常乳腺组织和6个乳腺炎乳腺组织中都出现了80kDa的蛋白条带,但是在第二个正常乳腺组织和第一个乳腺炎乳腺组织中出现了60kDa的蛋白条带。构建的CLU基因复合启动子表达载体pEGFP-N1-CMV-F2-X-CLU和pEGFP-N1-CMV-F2-Y-CLU分别转染乳腺上皮细胞进行乳腺组织体外表达显示只检测到X-CLU的mRNA表达,且蛋白分子量约60kDa,而Y-CLU没有表达。80kDa的蛋白可能是机体适应某种环境伴随X-CLU和Y-CLU两种蛋白的相互作用而形成的蛋白复合体。
4Clusterin基因3’UTR靶标确证奶牛乳腺炎抗性相关microRNA
本研究在CLU基因3’UTR区发现3个突变位点,生物信息分析发现+17301T缺失突变对miRNA的结合情况起关键作用。生产性能相关性研究显示+17301T突变与乳腺炎成正相关。CLU基因3’UTR在+17301T突变前结合bta-miR-2373,但T缺失后不结合。本研究中心基因芯片结果显示在中国荷斯坦牛乳腺炎乳腺组织中bta-miR-2373表达下调4.0倍。因此选择bta-miR-2373作为乳腺炎相关miRNA进行研究,实验证明,miRNA前体表达克隆载体CCS-bta2373-MR04在293T细胞中过表达,与CLU基因3’UTR靶标表达克隆载体pMIR-REPORT-miRNA-PT共转后,两者几乎完全结合,从而抑制CLU基因表达,CCS-bta2373-MR04也可以部分结合pMIR-REPORT-miRNA-PT-SNP降低CLU基因表达。因此,在乳腺炎发病过程中,降低内源性bta-miR-2373的表达,可上调CLU基因表达量,增强奶牛乳腺炎抗性。所以说,bta-miR-2373参与奶牛乳腺炎的发生和发展,可作为奶牛乳腺炎抗病育种的选择指标。
Bovine mastitis is a breast lesion caused by physical, chemical, or microbial stimulation. In cows, it can cause huge losses in milk production and is therefore of great importance in dairy farming. Although the symptoms and methods for prevention of mastitis in dairy cows have been studied for nearly a century with some effect, its pathogenic mechanisms are still largely unknown and thus the problem cannot be completely controlled. Here, we analyzed the role of clusterin as a potential mastitis resistance gene. We investigated the molecular mechanisms of clusterin gene regulation and its role in mastitis and milk production traits.
1Detection of single nucleotide polymorphisms (SNPs) in the bovine clusterin gene and their association with mastitis and milk production traits
In this study, we analyzed the association of the clusterin (CLU) gene with bovine mastitis and milk traits. By sequencing, we detected SNPs in the5'flanking region, coding region, and3'untranslated region (UTR) of the CLU gene. We then analyzed the identified polymorphisms and their haplotypes, as well as birth order, for association with mastitis and the milk production traits of more than1000Chinese Holstein cows. The milk production traits analyzed were:milk yield, milk fat, milk protein percentage, somatic cell count, lipoprotein ratio, total milk volume, total milk fat, total milk protein, and milk performance. We found that, although there is little genetic variation among Chinese Holstein cows, a+17301T deletion in the CLU gene3'UTR was associated with mastitis and could therefore be used as a marker. The previously reported haplotype HH4was not associated with any trait. The birth order effect was important:somatic cell count increased with more previous births and milk performance stopped improving after the fourth birth.
2In silico and functional analysis of the clusterin promoter
Next, we analyzed the5'flanking region of the bovine CLU gene by bioinformatics. We then cloned different fragments containing promoter (TATA box) fragments, transcription factor binding sites, and/or CpG islands into the pGL3-Basic luciferase expression vector. We then analyzed promoter activity after transfection into293T cells. We found that the F1promoter had very weak activity, and that the C994T polymorphism within it had no notable effect. However, the F2promoter had strong activity. We then generated enhanced green fluorescent protein (EGFP)-based expression vectors with different F2-related promoters (pEGFP-N1-CMV-CLU, pEGFP-N1-F2-CLU, and pEGFP-N1-CMV-F2-CLU) and transfected them into293T cells and mammary epithelial cells. We found that both the pEGFP-N1-F2-CLU and pEGFP-N1-CMV-F2-CLU constructs could stimulate high levels of CLU gene expression and activity in293T cells. Expression of the composite promoter vector, pEGFP-N1-CMV-F2-CLU, activated CLU gene expression the strongest, and we observed expressed CLU protein in the cytoplasm.
3Alternative splicing and expression of the clusterin gene in healthy and mastitis-infected mammary tissue in Chinese Holstein cows
We cloned and sequenced the CLU mRNAs identified in mastitis-affected mammary tissue to examine alternative splicing. We identified two alternative splice variants, X-CLU and Y-CLU. Moreover, a SNP in the coding region led to the loss of many shear sites and caused dramatic changes in the CLU mRNA secondary structure. Both the X-CLU and Y-CLU alternative splice variants were expressed in vivo in normal and mastitis-affected breast tissue, but the expression of X-CLU was increased significantly in mastitis. At the protein level, an80-kDa CLU band was present in normal and mastitis-affected breast tissue (n=6each) and a60-kDa band was observed in one sample of each. When we generated constructs specifically expressing either splice form (pEGFP-N1-CMV-F2-X-CLU and pEGFP-N1-CMV-F2-Y-CLU) and expressed them in mammary epithelial cells, we could detect expression of the X-CLU mRNA and the60-kDa protein, but not the Y-CLU mRNA or the80-kDa band. The Y-CLU-derived,80-kDa protein may be expressed only in certain environmental conditions, and may form protein complexes with the X-CLU-derived60-kDa protein.
4A clusterin SNP affecting microRNA binding is associated with mastitis in dairy cattle
Of the three variants we identified the3'UTR of the CLU gene, bioinformatics analysis of the mastitis-associated+17301T deletion suggested that this site may play an important role in microRNA (miRNA) binding. We found that the normal allele bound to bta-miR-2373, but that this binding was abolished in the presence of the+17301T deletion. Moreover, we demonstrated by gene-chip analysis that bta-miR-2373was downregulated four-fold in mastitis-affected breast tissue from Chinese Holstein cattle compared with in non-affected tissue. Study found that MicroRNA precursor expression cloning vector CCS-bta2373-MR04in293T cells overexpress, CLU gene3'UTR of target expression cloning vector pMIR-REPORT-miRNA-PT is almost can be fully combined with CCS-bta2373-MR04completely inhibit the bta-miR-2373expression, pMIR-REPORT-miRNA-PT-SNP can also be part of the combination CCS-bta2373-MR04and reduce the bta-miR-2373expression, resulting in mastitis pathogenesis in the up-regulation of CLU gene expression, participation in mastitis occurrence and development. We propose that the expression level of bta-miR-2373can be used as a mastitis resistance breeding selection marker in dairy cows.
引文
[1]程维杰,李秋玲,王长法,等.荷斯坦牛HSP70-1基因遗传多态性与乳腺炎抗性关系[J].遗传,2009(2)：169-74
[2]张利军,蔡亚非,刘庆华,等.奶牛乳铁蛋白基因启动子区PCR-RFLP分析与乳房炎的相关性[J].福建农林大学学报,2005,34(1)：87-91
[3]王洪梅,孔振兴,王长法,等.奶牛乳铁蛋白基因5’侧翼区遗传多态性及其与乳腺炎关联性分析[J].遗传,2009,31(4)：393-9
[4]Roosen S, Exner K, Paul S, et al. Bovine β-defensins:Identification and characterization of novel bovine β-defensin genes and their expression in mammary gland tissue [J]. Mammalian Genome,2004,15(10):834-42.
[5]Goldammer T, Zerbe H, Molenaar A, et al. Mastitis increases mammary mRNA abundance of P-defensin5, Toll-like-receptor2 (TLR2), and TLR4 but not TLR9 in cattle [J]. Clinical and Diagnostic Laboratory Immunology,2004, 11(1):174-85
[6]Mejdell CM, Lie 0, Solbu H, et al. Association of major histocompatibility complex antigens (BoLA-A) with Al bull progeny test results for mastitis, ketosis and fertility in Norwegian Cattle [J]. Animal Genetics,1994,25(2):99-104
[7]Oddgeirsson O, Simpson SP, Morgan ALG, et al. Relationship between the bovine major histocompatibility complex (BoLA), erythrocyte markers and susceptibility to mastitis in Icelandic cattle [J]. Animal Genetics,1988,19(1):11-6
[8]Sharif S, Mallard BA, Wilkie BN, et al. Associations of the bovine major histocompatibility complex DRB3 (BoLA-DRB3) alleles with occurrence of disease and milk somatic cell score in Canadian dairy cattle [J]. Animal Genetics,1998,29(3):185-93
[9]王兴平,许尚忠,马腾壑,等.牛TLR4基因的遗传多态性与乳房炎的关联分析[J].畜牧兽医学报,2007,38(2)：120-4
[10]李春苗,石万海,储明星,等.荷斯坦母牛TLR1基因多态性及其与体细胞评分关系[J].中国农业科学,2009,42(6)：2118-25
[11]Opsal MA, Vige DI, Hayes B, et al. Genomic organization and transcript profiling of the bovine toll-like receptor gene cluster TLR6-TLR1-TLR10 [J]. Gene,2006,384:45-50
[12]Yang Y, Li Q, Ju Z, et al. Three novel single-nucleotide polymorphisms of complement component 4 gene (C4A) in Chinese Holstein cattle and their associations with milk performance traits and CH50 [J]. Vet Immunol Immunopathol,2012,145(1-2):223-32.
[13]Swanson KM, Stelwagen K, Dobson J, et al. Transcriptome profiling of Streptococcus uberis-induced mastitis reveals fundamental differences between immune gene expression in the mammary gland and in a primary cell culture model [J]. J Dairy Sci,2009,92(1): 117-29.
[14]Blaschuk O, Burdzy K, Fritz IB. Purification and characterization of a cell-aggregating factor(clusterin), the major glycoprotein in ram rete testis fluid [J]. J Biol Chem,1983,25; 258(12):7714-20.
[15]Jones SE, Jomary C. Clusterin [J]. Int J Biochem Cell Biol.2002,34(5):427-31.
[16]Purrello M, Bettuzzi S, Di Pietro C, et al. The gene for SP-40,40, human homolog of rat sulfated glycoprotein 2, rat clusterin, and rat testosterone-repressed prostate message 2, maps to chromosome 8 [J]. Genomics,1991,10(1):151-6.
[17]Wong P, Taillefer D, Lakins J, et al. Molecular characterization of human TRPM-2/clusterin, a gene associated with sperm maturation, apoptosis and neurodegeneration [J]. Eur J Biochem,1994,221(3):917-25.
[18]Birkenmeier EH, Letts VA, Frankel WN, et al. Sulfated glycoprotein-2 (Sgp-2) maps to mouse chromosome 14 [J]. Mamm Genome,1993,4(2):131-2.
[19]Jordan-Starck TC, Lund SD, Witte DP, et al. Mouse apolipoprotein J:characterization of a gene implicated in atherosclerosis [J]. J Lipid Res,1994,35(2):194-210.
[20]Rose JK, Doms RW. Regulation of protein export from the endoplasmic reticulum [J]. Annu Rev Cell Biol,1988,4:257-88.
[21]Kapron JT, Hilliard GM, Lakins JN, et al. Identification and characterization of glycosylation sites in human serum Clusterin [J]. Protein Sci,1997,6 (10):2120-33.
[22]De Silva HV, Harmony JA, Stuart WD, Gil CM, Robbins J. Apolipoprotein J:structure and tissue distribution[J]. Biochemistry,1990; 29(22):5380-9.
[23]Wilson MR, Easterbrook-Smith SB. Clusterin is a secreted mammalian chaperone [J]. Trends Biochem Sci,2000,25(3):95-8.
[24]Lupas A, Van Dyke M, Stock J. Predicting coiled coils from protein sequences [J]. Science, 1991,252 (5010):1162-4.
[25]Lakins J, Bennett SA, Chen JH, et al. Clusterin biogenesis is altered during apoptosis in the regressing raventral prostate [J]. J Biol Chem,1998,273(43):27887-95.
[26]Kounnas MZ, Loukinova EB, Stefansson S, et al. Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin [J]. J Biol Chem,1995,270(22):13070-5.
[27]Leskov KS, Klokov DY, Li J, et al. Synthesis and functional analyses of nuclear clusterin, a cell death protein [J]. J Biol Chem.2003,28; 278(13):11590-600.
[28]Jin G, Howe PH. Transforming growth factor beta regulates clusterin gene expression via modulation of transcription factor c-Fos [J]. Eur J Biochem,1999,263(2):534-42.
[29]Yang CR, Leskov K, Hosley-Eberlein K, et al. Nuclear clusterin/XIP8, an x-ray-induced Ku70-binding protein that signals cell death [J]. Proc Natl Acad Sci U S A,2000,97(11): 5907-12.
[30]Reddy KB, Jin G, Karode MC, et al. Transforming growth factor beta (TGF beta)-induced nuclear localization of apolipoprotein J/clusterin in epithelial cells [J]. Biochemistry,1996, 35(19):6157-63.
[31]Michel D, Chatelain G, North S, et al. Stress-induced transcription of the clusterin/apo gene [J]. Biochem J,1997,328(Pt 1):45-50.
[32]Bayon Y, Ortiz MA, Lopez-Hernandez FJ, et al. The retinoid antagonist MX781 induces clusterin expression in prostate cancer cells via heat shock factor-1 and activator protein-1 transcription factors [J].Cancer Res,2004,64(16):5905-12.
[33]Zhou W, Janulis L, Park n, et al. A novel anti-proliferative property of clusterin in prostate cancer cells [J]. Life Sci,2002,72(1):11-21.
[34]Gutacker C, Klock G, Diel P, et al. Nerve growth factor and epidermal growth factor stimulate clusterin gene expression in PC12 cells [J]. Biochem J,1999,339(P3):759-66.
[35]Jenne DE, Tschopp J. Molecular structure and functional characterization of a human complement cytolysis inhibitor found in blood and seminal plasma:identity to sulfated glycoprotein 2, a constituent of rat testis fluid [J]. Proc Natl Acad Sci U S A,1989,86(18): 7123-7.
[36]Jenne DE, Lowin B, Peitsch MC, et al. Clusterin (complement lysis inhibitor)forms a high density lipoprotein complex with apolipoprotein A-I in human plasma [J]. J Biol Chem, 1991,266(17):11030-6.
[37]May PC. Sulfated glycoprotein-2:an emerging molecular marker for neurodegeneration [J]. Ann N Y Acad Sci,1993,679:235-44.
[38]Sylvester SR, Morales C, Oko R, et al. Localization of sulfated glycoprotein-2(clusterin)on spermatozoa and in the reproductive tract of the male rat [J]. Biol Reprod,1991,45(1): 195-207.
[39]Collard MW, Griswold MD. Biosynthesis and molecular cloning of sulfated glycoprotein 2 secreted by rat Sertoli cells [J]. Biochemistry,1987,26(12):3297-303.
[40]Atlas-White M, Murphy BF, Baker HW. Localisation of clusterin in normal human sperm by immunogold electron microscopy [J]. Pathology,2000,32(4):258-61.
[41]Hochgrebe TT, Humphreys D, Wilson MR, et al, A reexamination the role of clusterin as a complement regulator [J]. Exp Cell Res,1999,249(1):13-21.
[42]Murphy BF, Kirszbaum L, Walker ID, et al. SP-40,40, a newly identified norma human serum protein found in the SC5b-9 complex of complement and in the immune deposits in glomerulonephritis [J]. J Clin Invest,1988,81(6):1858-64.
[43]Danik M, Chabot JG, Mercier C, et al. Human gliomas and epileptic foci express high levels of a mRNA related to rat testicular sulfated glycoprotein 2, a purported marker of cell death [J]. Proc Natl Acad Sci U S A,1991,88(19):8577-81.
[44]Palmer DJ, Christie DL. Identification of molecular aggregates containing glycoproteins III, J, K (carboxypeptidase H) and H(Kex2-related proteases) in the soluble and membrane fractions of adrenal medullary chromaffin granules [J]. J Biol Chem,1992,267(28): 19806-12.
[45]Bartl MM, Luckenbach T, Bergner O, et al. Multiple receptors mediate apoJ-dependent clearance of cellular debris into nonprofessional phagocytes [J]. Exp Cell Res,2001,271(1): 130-41.
[46]Silkensen JR, Skubitz KM, Skubitz AP, et al. Clusterin promotes the aggregation and adhesion of renal porcine epithelial cells [J]. J Clin Invest,1995,96(6):2646-53.
[47]Fritz IB, Burdzy K, Setchell B, et al. Ram rete testis fluid contains a protein (clusterin) which influences cell-cell interactions in vitro [J]. Biol Reprod,1983,28(5):1173-88.
[48]Debure L, Vayssiere JL, Rincheval V, et al. Intracellula clusterin causes juxtanuclear aggregate formation and mitochondrial alteration [J]. J Cel Sci,2003,116(Pt 15):3109-21.
[49]Bettuzzi S, Scorcioni F, Astancolle S, et al. Clusterin(SGP-2) transient overexpression decreases proliferation rate of SV40-immortalized human prostate epithelial cells by slowing down cell cycle progression [J]. Oncogene,2002,21(27):4328-34.
[50]Scaltriti M, Santamaria A, Paciucci R, et al. Intracellular clusterin induces G2-M phase arrest and cell death in PC-3 prostate cancer cells [J]. Cancer Res,2004,64(17):6174-82.
[51]Matsuda A, Itoh Y, Koshikawa N, et al. Clusterin, an abundant serum factor, is a possible negative regulator of MT6-MMP/MMP-25 produced by neutrophils [J]. J Biol Chem,2003, 278(38):36350-7.
[52]Seiberg M, Marthinuss J. Clusterin expression within skin correlates with hair growth [J]. Dev Dyn,1995,202(3):294-301.
[53]Thomas-Salgar S, Millis AJ. Clusterin expression in differentiating smooth muscle cells [J]. J Biol Chem,1994,269(27):17879-85.
[54]Kirszbaum L, Sharpe JA, Murphy B, et al. Molecular cloning and characterization of the novel, human complement-associated protein, SP-40,40:a link between the complement and reproductive systems [J]. EMBO J,1989,8(3):711-8.
[55]Ghiggeri GM, Brusehi M, Candiano G, et al. DePletion of clusterin in renal diseases causing nephritic syndrome [J]. Kidney Int,2002,62(6):2184-94.
[56]Harr SD, Uint L, Hollister R, et al. Brain expression of apolipoproteins E, J, and A-1 in Alzheimer's disease [J]. J Neurochem,1996,66(6):2429-35.
[57]Gelissen IC, Hochgrebe T, Wilson MR, et al. Apolipoprotein J (clusterin) induces cholesterol export from macrophage-foam cells:a potential anti-atherogenic function? [J]. Biochem J, 1998,331 (Pt1):231-7.
[58]O'Bryan MK, Baker HWG, Saunders JR, et al. Human seminal clusterin (SP-40,40) [J]. J Clin Invest,1990,85(5):1477-86.
[59]Forni M, Zannoni A, Tamanini C, et al. Opposite regulation of clusterin and LH receptor in the swine corpus luteum during luteolysis [J]. Reprod Nutr Dev,2003,43(6):517-25.
[60]Bailey R, Griswold MD. Clusterin in the male reproductive system:localization and possible function [J]. Mol Cell Endocrinol,1999,151(1-2):17-23.
[61]Humphreys DT, Carver JA, Easterbrook-Smith SB, et al. Clusterin ha chaperone-like activity similar to that of small heat shock proteins [J]. J Biol Chem,1999,274(11):6875-81.
[62]Poon S, Rybchyn MS, Easterbrook-Smith SB, et al. Mildly acidic pH activates the extracellular molecular chaperone clusterin [J]. J Biol Chem,2002,18;277(42):39532-40.
[63]Lakins JN, Poon S, Easterbrook-Smith SB, et al. Evidence that clusterin has diserete chaperone and ligand binding sites [J]. Bioehemistry,2002,41(1):282-91.
[64]Wellmann A, Thieblemont C, Pittaluga S, et al. Detection of differentially expressed genes in lymphomas using cDNA arrays:identification of clusterin as a new diagnostic marker for anaplastic large-cell lymphomas [J]. Blood,2000,15; 96(2):398-404.
[65]Xin DQ, Zhu XH, Ai JK, et al. Prevention of cell death in LNCaP cells by overexpression of clusterin [J]. Beijing Da Xue Xue Bao,2004,36(2):154-58.
[66]Sklar GN, Eddy HA, Jacobs SC, et al. Combined antitumor effect of suramin plus irradiation in human prostate cancer cells:the role of apoptosis [J]. J Urol,1993,150(5 P1):1526-32.
[67]Warri AM, Huovinen RL, Laine AM, et al. Apoptosis in toremifene-induced growth inhibition of human breast cancer cells in vivo and in vitro [J]. J Natl Cancer Inst,1993,85(17): 1412-8.
[68]Koch-Brandt C, Morgans C. Clusterin:a role in cell survival in the face of apoptosis? [J]. Prog Mol Subcell Biol,1996,16:130-49.
[69]Trougakos IP, So A, Jansen B, et al. Silencing expression of the clusterin/apolipoprotein gene in human cancer cells using small interfering RNA induces spontaneous apoptosis, reduced growth ability, and cell sensitization to genotoxic and oxidative stress [J]. Cancer Res,2004, 64(5):1834-42.
[70]Redondo M, Tellez T, Roldan MJ, et al. Anticlusterin treatment of breast cancer cells increases chemotherapy-and tamoxifen-sensitivity and counteracts the inhibitory action of dexamethasone on chemotherapy-induced cytotoxicity [J]. Breast Cancer Res,2007, 9(6):R86.
[71]Trougakos IP, Gonos ES. Clusterin/apolipoprotein J in human aging and cancer [J]. Int J Biochem Cell Biol,2002,34(11):1430-48.
[72]Pucci S, Bonanno E, Pichiorri F, et al. Modulation of different clusterin isoforms in human colon tumorigenesis [J]. Oncogene,2004,23(13):2298-304.
[73]Yamada K, Hori Y, Hanaufsa N, et al. Clusterin is up-regulated in glomerular mesangial cells in complement-mediated injury [J]. Kidney Int,2001,59(1):137-46.
[74]Saunders JR, Aminian A, McRae JL, et al. Clusterin depletion enhances immune glomerular injury in the isolated perufsed kidney [J]. Kidney Int,1994,45(3):817-27.
[75]Sehlegel PN, Matthews GJ, Ciehon Z, et al. Clusterin Production in the obstructed rabbit kidney:correlations with loss of renal function [J]. J Am Soc Nephrol,1992,3(5):1163-71.
[76]Obermuller N, Gretz W, Woude FJ, et al. Differentiation and cell polarity during renal cyst formation in the Han:SPRD(cy/+)rat, a model for ADPKD [J]. Am J Physiol,1997,273(3 Pt 2):357-71.
[77]Choi-Miura NH, Oda T. Relationship between multifunctional protein "clusterin" and Alzheimer disease [J]. Neurobiol Aging,1996,17(5):717-22.
[78]McLaughlin L, Zhu G, Mistry M, et al. Apolipoprotein J/clusterin limits the severity of murine autoimmune myocarditis [J]. J Clin Invest,2000,106(9):1105-13.
[79]Moretti RM, Marelli MM, Mai S, et al. Clusterin Isoforms Differentially Affect Growth and Motility of Prostate Cells:Possible Implications in Prostate Tumorigenesis [J]. Cancer Res, 2007,67 (21):10325-33.
[80]Kruger S, Ola V, Fischer D, et al. Prognostic significance of clusterin immunoreactivity in breast cancer [J]. Neoplasma,2007,54(1):46-50.
[81]Shannan B, Seifert M, Leskov K, et al. Challenge and promise:roles for clusterin in pathogenesis, progression and therapy of cancer [J]. Cell Death Differ,2006,13 (1):12-9.
[1]Abnizova I, te Boekhorst R, Walter K, et al. Some statistical properties of regulatory DNA sequences and their use in predicting regulatory regions in the Drosophila genome:the fluffy-tail test [J]. BMC Bioinformatics,2005,6:1-9.
[2]Kimura K, Wakamatsu A, Suzuki Y, et al. Diversification of transcriptional modulation: Large-scale of human genes identification and characterization of putative alternative promoters [J]. Genome Res,2006,16(1):55-65.
[3]Schmitt-John T, Engels JW. Promoter constmctions for effieient seeretion expression in Streptomyces lividans [J]. APPI Mierobiol Bioteehnol,1992,36(4):493-98.
[4]Jocab P, Monod J. Genetic regulatory mechanisms in the synthesis of proteins. J Mol Biol, 1961,3:318-56.
[5]Wang Z, Huang J, Zhong J, et al. Molecular cloning, promoter analysis, SNP detection of Clusterin gene and their associations with mastitis in Chinese Holstein cows [J]. Mol Biol Rep,2012,39(3):2439-45.
[6]张利博。牛Nrampl基因5’端调控区的启动子功能和SNP分析[D]。吉林大学。2009。
[7]周磊。bLF基因部分序列的PCR-SSCP分析及其作为乳腺炎抗性分子标记的可行性研究[D]。南京农业大学,2006。
[8]张利军,蔡亚非,刘庆华,等。奶牛乳铁蛋白基因启动子区PCR-RFLP分析与乳房炎的相关性[J]。福建农林大学学报,2005,34(1)：84-91。
[9]李国华,张沅,孙东晓,等。奶牛乳铁蛋白基因5’侧翼区PCR-SSCP多态性分析[J]。遗传,2004,26(6)：827-30。
[10]王洪梅,孔振兴,王长法,等。奶牛乳铁蛋白基因5’侧翼区遗传多态性及其与乳腺炎关联性分析[J]。遗传,2009,31(4)：393-9。
[11]Kaminski S, Olenski K, Brym P, et al. Single nucleotide polymorphism in the promoter region of the lactoferrin gene and its associations with milk performance traits in polish Holstein-friesian cows [J]. Genetika,2006,42(8):111-20.
[12]Daly M, Ross P, Giblin L, et al. Polymorphisms within the lactoferrin gene promoter in various cattle breeds [J]. Anim Biotechnol,2006,17(1):33-42.
[13]Li GH, Zhang Y, Sun DX, et al. Study on the polymorphism of bovine lactoferrin gene and its relationship with mastitis [J]. Animal Biotechnol,2004,15(1):67-76.
[14]Hamalainen T, Poutanen M, Huhtaniemi I.Promoter function of different length of the murine luteinizing hormone recept or gene 5'-flanking region in transfected gonadal cells and in transgenic mice [J]. Endocrino logy,2001,142(6):2427-34.
[15]Ikram-ul-Haq, Ashraf H, Iqbal J, et al. Production of alpha amylase by Bacillus licheniformis using an economical medium [J]. Bioresource Technology,2003,87(1):57-61.
[16]Veloshinie G, Lise K. Evaluation of different formulations of Bacillus licheniformis in mango packs house trials [J]. Biological Control,2006,37:237-42.
[17]Elisa AM, Jacques BS. China flavour ester synthesis by a new esterase from Bacillus licheniformis [J]. Journal of Molecular Catalysis B:Enzymatic,2000,10:377-83.
[18]Pnar C, Tuncer H. Ozdamar.Mass flux balance-based model and metabolic pathway engineering analysis for serine alkaline protease synthesis by Bacillus licheniformis [J]. Enzyme and Microbial Technology,1999,24:621-35.
[19]Ritu S, Uwe T. Bomscheuer, et al. Synthesis of kyotorphin precursor by anorganic solvent-stable protease from Bacillus lichenifor mis RSP-09-37 [J]. Journal of Molecular Catalysis B:Enzymatic,2004,32:1-5.
[20]Chow LT, Gelinas RE, Broker TR, et al. An amazing sequence arrangement at the 5'nds of adenovirus 2 messenger RNA [J]. Cell,1977,12(1):1-8.
[21]Gilbert W. Why genes in pieces? [J]. Nature,1978,271(5645):501.
[22]Choi E, Kuehl M, Wall R. RNA splicing generates a variant light chain from an aberrantly rearranged kappa gene [J]. Nature,1980,286(5775):776-9.
[23]Kramer A. The structure and function of proteins involved in mammalian pre-mRNA splicing [J]. Annu Rev Biochem,1996,65:367-409.
[24]Black DL. Mechanisms of alternative pre-messenger RNA splicing [J]. Annu Rev Biochem, 2003,72:291-336.
[25]Surono A, Takeshima Y, Wibawa T, et al. Circular dystrophin RNAs consisting of exons that were skipped by alternative splicing [J]. Hum Mol Genet,1999,8(3):493-500.
[26]Shapiro MB, Senapathy P. RNA splice junctions of different classes of eukaryotes:sequence statistics and functional implications in gene expression [J]. Nucleic Acids Res,1987,15 (17):7155-74.
[27]Aebi M, Hornig H, Weissmann C.5'cleavage site in eukaryotic pre-mRNA splicing is determined by the overall 5'splice region, not by the conserved 5'GU [J]. Cell,1987,50(2): 237-46.
[28]Zhang W, Liu H, Han K, et al. Region-specific alternative splicing in the nervous system: implications for regulation by the RNA-binding protein NAPOR [J]. RNA,2002,8(5): 671-85.
[29]Nilsen TW. The spliceosome:no assembly required? [J]. Mol Cell,2002,9(1):8-9.
[30]Staley JP, Guthrie C. Mechanical devices of the spliceosome:motors, clocks, springs, and things [J]. Cell,1998,92(3):315-26.
[31]Brow DA. Allosteric cascade of spliceosome activation [J]. Annu Rev Genet,2002,36: 333-60.
[32]Das R, Zhou Z, Reed R. Functional association of U2 snRNP with the ATP-independent spliceosomal complex E [J]. Mol Cell,2000, (5):779-87.
[33]Nilsen TW. A parallel spliceosome [J]. Science,1996,273(5283):1813.
[34]Tsai RT, Fu RH, Yeh FL, et al. Spliceosome disassembly catalyzed by Prp43 and its associated components Ntrl and Ntr2 [J]. Genes Dev,2005,19(24):2991-3003.
[35]Ladd AN, Cooper TA. Finding signals that regulate alternative splicing in the post-genomic era [J]. Genome Biol,2002,3(11):0008.
[36]Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome [J]. Nature,2001,409 (6822):860-921.
[37]Soret J, Gabut M, Tazi J. SR proteins as potential targets for therapy [J]. Prog Mol Subcell Biol,2006,44:65-87.
[38]Simard MJ, Chabot B. SRp30c is a repressor of 3'splice site utilization [J]. Mol Cell Biol, 2002,22(12):4001-10.
[39]Caceres JF, Kornblihtt AR. Alternative splicing:multiple control mechanisms and involvement in human disease [J]. Trends Genet,2002,18(4):186-93.
[40]Li Y, Blencowe BJ. Distinct factor requirements for exonic splicing enhancer function and binding of U2AF to the polypyrimidine tract [J]. J Biol Chem,1999,274(49):35074-9.
[41]Cote J, Dupuis S, Jiang Z, et al. Caspase-2 pre-mRNA alternative splicing:Identification of an intronic element containing a decoy 3'acceptor site [J]. Proc Natl Acad Sci USA,2001, 98(3):938-43.
[42]Stamm S. Signals and their transduction pathways regulating alternative splicing:a new dimension of the human genome [J]. Hum Mol Genet,2002,11(20):2409-16.
[43]Smith CW, Valcarcel J. Alternative pre-mRNA splicing:the logic of combinatorial control [J]. Trends Biochem Sci,2000,25(8):381-8.
[44]Li B, Wachtel C, Miriami E, et al. Stop codons affect 5'splice site selection by surveillance of splicing [J]. Proc Natl Acad Sci USA,2002,99(8):5277-82.
[45]Goldstrohm AC, Greenleaf AL, Garcia-Blanco MA. Co-transcriptional splicing of pre-messenger RNAs:considerations for the mechanism of alternative splicing [J]. Gene,2001, 277(1-2):31-47.
[46]Fuller-Pace FV. DExD/H box RNA helicases:multifunctional proteins with important roles in transcriptional regulation [J]. Nucleic Acids Res,2006,34(15):4206-15.
[47]Konig H, Ponta H, Herrlich P. Coupling of signal transduction to alternative pre-mRNA splicing by a composite splice regulator [J]. EMBO J,1998,17(10):2904-13.
[48]Lynch KW, Weiss A. A model system for activation-induced alternative splicing of CD45 pre-mRNA in T cells implicates protein kinase C and Ras [J]. Mol Cell Biol,2000,20 (1): 70-80.
[49]Tacke R, Mauley JL. Determinants of SR protein specificity [J]. Curr Opin Cell Biol,1999, 11(3):358-62.
[50]McVety S, Li L, Gordon PH, et al. Disruption of an exon splicing enhancer in exon 3 of MLH1 is the cause of HNPCC in a Quebec family [J]. J Med Genet,2006,43(2):153-6.
[51]Kawase T, Akatsuka Y, Torikai H, et al. Alternative splicing due to an intronic SNP in HMSD generates a novel minor histocompatibility antigen [J]. Blood,2007,110(3): 1055-63.
[52]Douglas KB, Windels DC, Zhao J, et al. Complement receptor 2 polymorphisms associated with systemic lupus erythematosus modulate alternative splicing [J]. Genes Immun,2009, 10(5):457-69.
[53]Hirose Y, Chiba K, Karasugi T, et al. A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation [J]. Am J Hum Genet,2008,82(5):1122-9.
[54]Murani E, Ponsuksili S, Seyfert HM, et al. Dual effect of a single nucleotide polymorphism in the first intron of the porcine secreted phosphoprotein 1 gene:allele-specific binding of C/EBP beta and activation of aberrant splicing [J]. BMC Mol Biol,2009,21; 10:96.
[55]Carlini DB, Genut JE. Synonymous SNPs provide evidence for selective constraint on human exonic splicing enhancers [J]. J Mol Evol,2006,62(1):89-98.
[56]ElSharawy A, Manaster C, Teuber M, et al. SNPSplicer:systematic analysis of SNP-dependent splicing in genotyped cDNAs [J]. Hum Mutat,2006,27(11):1129-34.
[57]Zhang Y, Bertolino A, Fazio L, et al. Polymorphisms in human dopamine D2 receptor gene affect gene expression, splicing, and neuronal activity during working memory [J]. Proc Natl Acad Sci USA,2007,18; 104(51):20552-7.
[58]Harari A, Ooms M, Mulder LC, et al. Polymorphisms and splice variants influence the antiretroviral activity of human APOBEC3H [J]. J Virol,2009,83(1):295-303.
[59]Paris AJ, Snapir Z, Christopherson CD, et al. A polymorphism that delays fibrosis in hepatitis C promotes alternative splicing of AZIN1, reducing fibrogenesis [J]. Hepatology,2011, 54(6):2198-207.
[60]Guyon-Debast A, Lecureuil A, Bonhomme S, et al. A SNP associated with alternative splicing of RPT5b causes unequal redundancy between RPT5a and RPT5b among Arabidopsis thaliana natural variation [J]. BMC Plant Biol,2010 Aug 3; 10:158.
[61]Modrek B, Lee C. A genomic view of alternative splicing [J]. Nat Genet,2002,30(1):13-9.
[62]Graveley BR. Alternative splicing:increasing diversity in the proteomic world [J]. Trends Genet,2001,17(2):100-7.
[63]Black DL. Protein diversity from alternative splicing:a challenge for bioinformatics and post-genome biology [J]. Cell,2000,103(3):367-70.
[64]Grabowski PJ, Black DL. Alternative RNA splicing in the nervous system [J]. Prog Neurobiol, 2001,65(3):289-308.
[65]Cogan JD, Phillips JA, Schenkman SS, et al. Familial growth hormone deficiency:a model of dominant and recessive mutations affecting a monomeric protein [J]. J Clin Endocrinol Metab,1994,79(5):1261-5.
[66]Moseley CT, Mullis PE, Prince MA, et al. An exon splice enhancer mutation causes autosomal dominant GH deficiency [J]. J Clin Endocrinol Metab,2002,87(2):847-52.
[67]Zhou Z, Licklider LJ, Gygi SP, et al. Comprehensive proteomic analysis of the human spliceosome [J]. Nature,2002,12; 419(6903):182-5.
[68]Makarova OV, Makarov EM, Liu S, et al. Protein 61K, encoded by a gene (PRPF31) linked to autosomal dominant retinitis pigmentosa, is required for U4/U6*U5 tri-snRNP formation and pre-mRNA splicing [J]. EMBO J,2002,1;21(5):1148-57.
[69]Liquori CL, Ricker K, Moseley ML, et al. Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9 [J]. Science,2001,3; 293(5531):864-7.
[70]Savkur RS, Philips AV, Cooper TA. Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy [J]. Nat Genet,2001, 29(1):40-7.
[71]Charlet-B N, Savkur RS, Singh G, et al. Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing [J]. Mol Cell,2002,10(1): 45-53.
[72]Nissim-Rafinia M, Kerem B. Splicing regulation as a potential genetic modifier [J]. Trends Genet,2002,18(3):123-7.
[73]Sorek R, Basechess O, Safer HM. Computational analysis and experimental validation of tumor-associated alternative RNA splicing in human cancer [J]. Cancer Res,2003,63(20): 655-7.
[74]Sneath RJ, Mangham DC. The normal structure and function of CD44 and its role in neoplasia [J]. Mol Pathol,1998,51(4):191-200.
[75]Heider KH, Kuthan H, Stehle G, et al. CD44v6:a target for antibody-based cancer therapy [J]. Cancer Immunol Immunother,2004,53(7):567-79.
[76]Gargani M, Valentini A, Pariset L. A novel point mutation within the EDA gene causes an exon dropping in mature RNA in Holstein Friesian cattle breed affected by X-linked anhidrotic ectodermal dysplasia [J]. BMC Vet Res,2011,8; 7:35.
[77]王兴平,罗仍卓么,许尚忠,等。牛IRAK2基因有两种选择性剪接表达产物[J]。中国生物化学与分子生物学报,2009,25(3)：292-6。
[78]Huang JM, Wang ZY, Ju ZH, et al. Two splice variants of the bovine lactoferrin gene identified in Staphylococcus aureus isolated from mastitis in dairy cattle [J]. Genet Mol Res, 2011,21; 10(4):3199-203.
[79]Ju Z, Wang C, Li Q, et al. Alternative splicing and mRNA expression analysis of bovine SLAMF7 gene in healthy and mastitis mammary tissues [J]. Mol Biol Rep,2012,39(4): 4155-61.
[80]Hou Q, Huang J, Ju Z,et al. Identification of Splice Variants, Targeted MicroRNAs and Functional Single Nucleotide Polymorphisms of the BOLA-DQA2 Gene in Dairy Cattle [J]. DNA Cell Biol,2011,15.
[81]Wang Z, Huang J, Xia P,et al. Alternative splicing and expression of cattle clusterin gene in healthy and mastitis-infected mammary tissues [J]. J. Anim.Sci.Adv,2012,2(4).
[82]David PB. MicroRNAs:Genomics, biogenesis, mechanism and function [J]. Cell,2004, 116(2):281-297.
[83]Hutvagner G, Zamore PD. A microRNA in a multi-ple-turnover RNAi enzyme complex [J]. Science,2002,297(5589):2056-60.
[84]Zeng Y, Yi R, Cullen BR. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci USA [J].2003,100(17):9779-84.
[85]Doench JG, Peterson CP, Sharp PA. siRNAs can function as miRNAs [J]. Genes & Development,2003,17(4):438-42.
[86]Chen F, Yin QW. MiRNAs regulate the gene expression [J]. Chinese Science Bulletin,2005, 50(13):1289-99.
[87]Ambros V, Bartel B, Bartel DP, et al. A uniform system for microRNA annotation [J]. RNA, 2003,9(3):277-9.
[88]Berezikov E, Cuppen E, Plasterk RH. Approaches to mi-croRNA discovery [J]. Nature Genetics,2006,38:2-7.
[89]Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 [J]. Cell,1993,75(5):843-54.
[90]Reinhart BJ, Slack FJ, Basson M, et al. The 21 nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans [J]. Nature,2000,403(6772):901-6.
[91]Johnston RJ, Hobert O. A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans [J]. Nature,2003,426(6968):845-9.
[92]Chang S, Johnston RJ Jr, Frokjaer-Jensen C, et al. MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode [J]. Nature,2004, 430(7001):785-9.
[93]Krichevsky AM, King KS, Donahue CP, et al. A microRNA array reveals extensive regulation of microRNAs during brain development [J]. RNA,2004,10(3):551:1274-81.
[94]Xu P, Vernooy SY, Guo M, et al. The Drosophila microRNA mir-14 suppresses cell death and is required for normal fat metabolism [J]. Current Biology,2003,13(9):790-5.
[95]Clop A, Marcq F, Takeda H, et al. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep [J]. Nature Genetics,2006, 38(7):813-8.
[96]Michael MZ, O'Connor SM, van Ho1st Pellekaan NG, et al. Reduced accumulation of specific microRNAs in colorectal neoplasia [J]. Mol Cancer Res,2003,1(12):882-91.
[97]Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13ql4 in chronic lymphocytic leukemia [J]. Proc Natl Acad Sci USA,2002,99(24):15524-9.
[98]Takamizawa J, Konishi H, Yanagisawa K, et al. Reduced expressionof the let-7 microRNAs in human lung cancers in association with shortened postoperative survival [J]. Cancer Research,2004,64 (11):3753-6.
[99]Volinia S, Calin GA, Liu CG, et al. A microRNA expression signature of human solid tumors defines cancer gene targets [J]. PNAS,2006,103(7):2257-61.
[100]Taganov KD, Boldin MP, Chang KJ, et al. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses [J]. Proc Natl Acad Sci USA.2006,15; 103(33):12481-6.
[101]Wu H, Neilson JR, Kumar P, et al. miRNA profiling of nai've, effector and memory CD8 T cells [J]. PLoS One,2007,10; 2(10):e1020.
[102]Sonkoly E, Pivarcsi A. Advances in microRNAs:implications for immunity and inflammatory diseases [J]. J Cell Mol Med,2009,13(1):24-38.
[103]Hata T, Murakami K, Nakatani H, et al. Isolation of bovine milk-derived microvesicles carrying mRNAs and microRNAs [J]. Biochem Biophys Res Commun,2010,28; 396(2): 528-33.
[104]Kosaka N, Izumi H, Sekine K, et al. microRNA as a new immune-regulatory agent in breast milk [J]. Silence,2010,1; 1(1):7.
[105]Zhou Q, Li M, Wang X, et al. Immune-related microRNAs are abundant in breast milk exosomes [J]. Int J Biol Sci,2012,8(1):118-23.
[106]Chen X, Gao C, Li H, et al. Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products [J]. Cell Res,2010,20(10):1128-37.
[107]Coutinho LL, Matukumalli LK, Sonstegard TS, et al. Discovery and profiling of bovine microRNAs from immune-related and embryonic tissues [J]. Physiol Genomics,2007,14; 29(1):35-43.
[108]Gu Z, Eleswarapu S, Jiang H. Identification and characterization of microRNAs from the bovine adipose tissue and mammary gland [J]. FEBS Lett,2007,6; 581(5):981-8.
[109]Feuermann Y, Robinson GW, Zhu BM, et al. The miR-17/92 cluster is targeted by STAT5 but dispensable for mammary development [J]. Genesis,2012,2:10.1002.
[110]Hata T, Murakami K, Nakatani H, et al. Isolation of Bovine Milk-Derived Microvesicles Carrying mRNAs and microRNAs [J]. Biochem Biophys Res Commun,2010,396:528-33.
[111]李惠侠,王振云,张震,等。高温条件下miRNA-24对奶牛乳腺上皮细胞增殖与凋亡的影响[J]。中国农业科学,2010,43(22)：4732-38。
[112]万中英,佟慧丽,李庆章,等。中药王不留行增乳活性单体及催乳素对奶牛乳腺上皮细胞特异性miRNA的影响[J]。中国畜牧兽医,2010,37(8)：230-2。
[113]Jiang S, Zhang HW, Lu MH, et al. MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene [J]. Cancer Res,2010,70(8): 3119-27.
[114]Li H, Bian C, Liao L, et al. miR-17-5p promotes human breast cancer cell migration and invasion through suppression of HBP1 [J]. Breast Cancer Res Treat,2011,126(3):565-75.
[115]Wright JA, Richer JK, Goodall GJ. MicroRNAs and EMT in mammary cells and breast cancer [J]. J Mammary Gland Biol Neoplasia,2010,15(2):213-23.
[116]Tavazoie SF, Alarcon C, Oskarssoon T, et al. Endogenous human microRNAs that suppress breast cancer metastasis [J]. Nature,2008,451(7175):147-52.
[117]Sempere LF, Christensen M, Silahtaroglu A, et al. Altered microRNA expression confined to specific epithelial cell subpopulations in breast cancer [J]. Cancer Res,2007,67(24): 11612-20.
[118]Horikawa Y, Wood CG, Yang HS, et al. Single nucleotide polymorphisms of microRNA machinery genes modify the risk of renal cell carcinoma [J]. Clin Cancer Res,2008,14(23): 7956-62.
[119]Yang HS, Dinney CP, Ye YQ,et al. Evaluation of genetic variants in microRNA-related genes and risk of bladder cancer [J]. Cancer Res,2008,68(7):2530-7.
[120]Gottwein E, Cai XZ, Cullen BR. A novel assay for viral microRNA function identifies a single nucleotide polymorphism that affects Drosha processing [J]. J Virol,2006,80(11): 5321-6.
[121]Duan RH, Pak CH, Jin P. Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA [J]. Hum Mol Genet,2007,16(9):1124-31.
[122]Mencia A, Modamio-Hoybjor S, Redshaw N, et al. Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss [J]. Nat Genet,2009, 41(5):609-13.
[123]Li W, Duan R, Kooy F, et al.Germline mutation of microRNA-125a is associated with breast cancer [J]. J Med Genet,2009,46(5):358-60.
[124]Kontorovich T, Levy A, Korostishevsky M,et al. Single nucleotide polymorphisms in miRNA binding sites and miRNA genes as breast/ovarian cancer risk modifiers in Jewish high-risk women [J]. Int J Cancer,2010,127(3):589-97.
[125]Iorio MV, Visone R, Dileva G, et al. MicroRNA signatures in human ovarian cancer [J]. Cancer Res,2007,67(18):8699-707.
[126]Bandres E, Agirre X, Bitarte N, et al. Epigenetic regulation of microRNA expression in colorectal cancer [J]. Int J Cancer,2009,125(11):2737-43.
[127]Chayka O, Corvetta D, Dews M, et al. Clusterin, a haploinsufficient tumor suppressor gene in neuroblastomas [J]. J Natl Cancer Inst,2009,6; 101(9):663-7.
[128]Figure 2-lto 2-6. Molecular Biology of the Gene.
[1]Zhang CK, Lin W, Cai YN, et al. Characterization of the genomic structure and tissue-specific promoter of the human nuclear receptor NR5A2 (hB1F) gene [J]. Gene,2001,8; 273 (2): 239-49.
[2]Makova KD, Ramsay M, Jenkins T, et al. Human DNA sequence variation in a 6.6-kb region containing the melanocortin 1 receptor promoter [J]. Genetics,2001,158 (3):1253-68.
[3]Nott A, Meislin SH, Moore MJ.A quantitative analysis of intron effects on mammalian gene expression [J]. RNA,RNA,2003,9(5):607-17.
[4]Zan LS, Zhang JL, Liu XW. Association study on AGPAT6 intron3 polym-orphism and milk performance of dairy cattle [J].Scientia Agricultura Sinica,2007,40(7):1498-1503.
[5]Ando Z, Sato S, Ikeda K, et al. Slc12a2 is a direct target of two closely related homeobox proteins, Sixl and Six4 [J]. FFBS J,2005,272(12):3026-41.
[6]Kumar JP. The sine oculis homeobox (SIX) family of transcription factors as regulators of development and disease [J]. Cell Mol Life Sci,2009,66(4):565-83.
[7]Hariri AR, Mattay VS, Tessitore A et al. Serotonin transporter genetic variation and the response of the human amygdale [J]. Science,2002,19,297 (5580):400-3.
[8]Kitamura A, Hasegawa G, Obayashi H, et al. Interleukin-6 polymorphism (-634C/G) in the promotor region and the progression of diabetic nephropathy in type 2 diabetes [J]. Diabet Med,2002,19 (12):1000-5.
[9]Fallin D, Cohen A, Essioux L, et al. Genetic analysis of case/control data using estimated haplotype frequencies:application to APOE locus variation and Alzheimer's disease [J]. Genome Res,2001,11(1):143-151.
[10]Liu W, Wang J, Li Q, et al. Correlation analysis between three novel SNPs of the Src gene in bovine and milk production traits [J]. Mol Biol Rep,2010,37(8):3771-7.
[11]Wang Z, Wang G, Huang J, et al. Novel SNPs in the ATP1B2 gene and their associations with milk yield, milk composition and heat-resistance traits in Chinese Holstein cows [J]. Mol Biol Rep,2011,38(3):1749-55.
[1]Abnizova I, Boekhorst R, Walter K, et al. Some statistical properties of regulatory DNA sequences and their use in predicting regulatory regions in the Drosophila genome:the fluffy-tail test [J]. BMC Bioinformatics,2005,27(6):109.
[2]L i D, Firozi PF, Wang LE, et al. Sensitivity to DNA damage induced by benzo (a) pyrene diol epoxide and risk of lung cancer:a case-control analysis [J]. Cancer Res,2001,61(4): 1445-50.
[3]Xuan Z, Zhao F, Wang J, et al. Genome-wide promoter extraction and analysisin human, mouse and rat. Genome Biol [J].2005,6(8):R72.
[4]Purrello M, Bettuzzi S, Di Pietro C, et al. The gene for SP-40,40, human homolog of rat sulfated glycoprotein 2, rat clusterin, and rat testosterone-repressed prostate message 2, maps to chromosome 8 [J]. Genomics,1991,10(1):151-6.
[5]Michel D, Chatelain G, North S, et al. Stress-induced transcription of the clusterin/apoJ gene [J]. Biochem J,1997,328:45-50.
[6]刘召华,郭洪年,郑光宇,等。ACA基因启动子的克隆及功能初探[J].生物工程学报。2005,25(1)：139-143。
[7]杨咏梅,曹英林,梁晓红,等。hTERT启动子调控的TRAIL基因载体的构建及表达[J].山东大学学报(医学版),2005,1：22-26.
[8]Hamalainen T, Poutanen M, Huhtaniemi I. Promoter function of different length of the murine luteinizing hormone recept or gene 5'2flanking region in transfected gonadal cells and in transgenic mice [J]. Endocrino logy,2001,142(6):2427-34.
[9]JACOB F, MONOD J. Genetic regulatory mechanisms in the synthesis of proteins [J]. J Mol Biol,1961,3:318-56.
[1]Matlin AJ, Clark F, Smith CW. Understanding alternative splicing:towards a cellular code [J]. Nat Rev Mol Cell Biol,6(5):386-98.
[2]Srebrow A, Komblihtt AR. The connection between splicing and cancer [J]. J Cell Sci,2006, 119(13):2635-41.
[3]Chacko E, Ranganathan S.Genome-wide analysis of alternative splicing in cow:implications in bovine as a model for human diseases [J]. BMC Genomics,2009,10(3):S11.
[4]Caceres JF, Komblihtt AR. Alternative Splicing:multiple control mechanisms and involvement in human disease [J]. Trends Genet,18(4):186-93.
[5]Jones SE, Jomary C. Clusterin [J]. Int J Biochem Cell Biol.2002,34(5):427-31.
[6]Swanson KM, Stelwagen K, Dobson J, et al. Transcriptome profiling of Streptococcus uberis-induced mastitis reveals fundamental differences between immune gene expression in the mammary gland and in a primary cell culture model [J]. J Dairy Sci.2009,92(1):117-29.
[7]French LE, Wohlwend A, Sappino AP, et al. Human clusterin gene expression is confined to surviving cells during in vitro programmed cell death [J]. J Clin Invest,1994,93(2):877-84.
[8]Yang CR, Leskov K, Hosley-Eberlein K, et al. Nuclear clusterin/XIP8, an x-ray-induced Ku70-binding protein that signals cell death [J]. Proc Natl Acad Sci USA,2000,97(11): 5907-12.
[1]Carrington JC, Ambros V. Role of microRNAs in plant and animal development [J]. Science, 2003,301(5631):336-8.
[2]Bartel DP. MicroRNAs:Genomics, Biogenesis, Mechanism, and Function [J]. Cell,2004,23; 116(2):281-97
[3]Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation:MicroRNAs can up-regulate translation [J]. Science.2007,21; 318(5858):1931-4.
[4]Fang Z, Rajewsky N. The impact of miRNA target sites in coding sequences and in 3'UTRs [J]. PLoS One,2011,22; 6(3):e18067.
[5]Liao Y, Du X, Lonnerdal B. miR-214 regulates lactoferrin expression and pro-apoptotic function in mammary epithelial cells [J]. J Nutr,2010,140(9):1552-6.
[6]Ambros V, Bartel B, Bartel DP, et al. A uniform system for microRNA annotation [J]. RNA, 2003,9(3):277-9.
[7]Berezikov E, Cuppen E, Plasterk RH. Approaches to microRNA discovery [J]. Nature Genetics,2006,38:S2-S7.
[8]Chayka O, Corvetta D, Dews M, et al. Clusterin, a haploinsufficient tumor suppressor gene in neuroblastomas [J]. J Natl Cancer Inst,2009,6;101(9):663-77.
[2]张利军,蔡亚非,刘庆华,等.奶牛乳铁蛋白基因启动子区PCR-RFLP分析与乳房炎的相关性[J].福建农林大学学报,2005,34(1)：87-91
[3]王洪梅,孔振兴,王长法,等.奶牛乳铁蛋白基因5’侧翼区遗传多态性及其与乳腺炎关联性分析[J].遗传,2009,31(4)：393-9
[4]Roosen S, Exner K, Paul S, et al. Bovine β-defensins:Identification and characterization of novel bovine β-defensin genes and their expression in mammary gland tissue [J]. Mammalian Genome,2004,15(10):834-42.
[5]Goldammer T, Zerbe H, Molenaar A, et al. Mastitis increases mammary mRNA abundance of P-defensin5, Toll-like-receptor2 (TLR2), and TLR4 but not TLR9 in cattle [J]. Clinical and Diagnostic Laboratory Immunology,2004, 11(1):174-85
[6]Mejdell CM, Lie 0, Solbu H, et al. Association of major histocompatibility complex antigens (BoLA-A) with Al bull progeny test results for mastitis, ketosis and fertility in Norwegian Cattle [J]. Animal Genetics,1994,25(2):99-104
[7]Oddgeirsson O, Simpson SP, Morgan ALG, et al. Relationship between the bovine major histocompatibility complex (BoLA), erythrocyte markers and susceptibility to mastitis in Icelandic cattle [J]. Animal Genetics,1988,19(1):11-6
[8]Sharif S, Mallard BA, Wilkie BN, et al. Associations of the bovine major histocompatibility complex DRB3 (BoLA-DRB3) alleles with occurrence of disease and milk somatic cell score in Canadian dairy cattle [J]. Animal Genetics,1998,29(3):185-93
[9]王兴平,许尚忠,马腾壑,等.牛TLR4基因的遗传多态性与乳房炎的关联分析[J].畜牧兽医学报,2007,38(2)：120-4
[10]李春苗,石万海,储明星,等.荷斯坦母牛TLR1基因多态性及其与体细胞评分关系[J].中国农业科学,2009,42(6)：2118-25
[11]Opsal MA, Vige DI, Hayes B, et al. Genomic organization and transcript profiling of the bovine toll-like receptor gene cluster TLR6-TLR1-TLR10 [J]. Gene,2006,384:45-50
[12]Yang Y, Li Q, Ju Z, et al. Three novel single-nucleotide polymorphisms of complement component 4 gene (C4A) in Chinese Holstein cattle and their associations with milk performance traits and CH50 [J]. Vet Immunol Immunopathol,2012,145(1-2):223-32.
[13]Swanson KM, Stelwagen K, Dobson J, et al. Transcriptome profiling of Streptococcus uberis-induced mastitis reveals fundamental differences between immune gene expression in the mammary gland and in a primary cell culture model [J]. J Dairy Sci,2009,92(1): 117-29.
[14]Blaschuk O, Burdzy K, Fritz IB. Purification and characterization of a cell-aggregating factor(clusterin), the major glycoprotein in ram rete testis fluid [J]. J Biol Chem,1983,25; 258(12):7714-20.
[15]Jones SE, Jomary C. Clusterin [J]. Int J Biochem Cell Biol.2002,34(5):427-31.
[16]Purrello M, Bettuzzi S, Di Pietro C, et al. The gene for SP-40,40, human homolog of rat sulfated glycoprotein 2, rat clusterin, and rat testosterone-repressed prostate message 2, maps to chromosome 8 [J]. Genomics,1991,10(1):151-6.
[17]Wong P, Taillefer D, Lakins J, et al. Molecular characterization of human TRPM-2/clusterin, a gene associated with sperm maturation, apoptosis and neurodegeneration [J]. Eur J Biochem,1994,221(3):917-25.
[18]Birkenmeier EH, Letts VA, Frankel WN, et al. Sulfated glycoprotein-2 (Sgp-2) maps to mouse chromosome 14 [J]. Mamm Genome,1993,4(2):131-2.
[19]Jordan-Starck TC, Lund SD, Witte DP, et al. Mouse apolipoprotein J:characterization of a gene implicated in atherosclerosis [J]. J Lipid Res,1994,35(2):194-210.
[20]Rose JK, Doms RW. Regulation of protein export from the endoplasmic reticulum [J]. Annu Rev Cell Biol,1988,4:257-88.
[21]Kapron JT, Hilliard GM, Lakins JN, et al. Identification and characterization of glycosylation sites in human serum Clusterin [J]. Protein Sci,1997,6 (10):2120-33.
[22]De Silva HV, Harmony JA, Stuart WD, Gil CM, Robbins J. Apolipoprotein J:structure and tissue distribution[J]. Biochemistry,1990; 29(22):5380-9.
[23]Wilson MR, Easterbrook-Smith SB. Clusterin is a secreted mammalian chaperone [J]. Trends Biochem Sci,2000,25(3):95-8.
[24]Lupas A, Van Dyke M, Stock J. Predicting coiled coils from protein sequences [J]. Science, 1991,252 (5010):1162-4.
[25]Lakins J, Bennett SA, Chen JH, et al. Clusterin biogenesis is altered during apoptosis in the regressing raventral prostate [J]. J Biol Chem,1998,273(43):27887-95.
[26]Kounnas MZ, Loukinova EB, Stefansson S, et al. Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin [J]. J Biol Chem,1995,270(22):13070-5.
[27]Leskov KS, Klokov DY, Li J, et al. Synthesis and functional analyses of nuclear clusterin, a cell death protein [J]. J Biol Chem.2003,28; 278(13):11590-600.
[28]Jin G, Howe PH. Transforming growth factor beta regulates clusterin gene expression via modulation of transcription factor c-Fos [J]. Eur J Biochem,1999,263(2):534-42.
[29]Yang CR, Leskov K, Hosley-Eberlein K, et al. Nuclear clusterin/XIP8, an x-ray-induced Ku70-binding protein that signals cell death [J]. Proc Natl Acad Sci U S A,2000,97(11): 5907-12.
[30]Reddy KB, Jin G, Karode MC, et al. Transforming growth factor beta (TGF beta)-induced nuclear localization of apolipoprotein J/clusterin in epithelial cells [J]. Biochemistry,1996, 35(19):6157-63.
[31]Michel D, Chatelain G, North S, et al. Stress-induced transcription of the clusterin/apo gene [J]. Biochem J,1997,328(Pt 1):45-50.
[32]Bayon Y, Ortiz MA, Lopez-Hernandez FJ, et al. The retinoid antagonist MX781 induces clusterin expression in prostate cancer cells via heat shock factor-1 and activator protein-1 transcription factors [J].Cancer Res,2004,64(16):5905-12.
[33]Zhou W, Janulis L, Park n, et al. A novel anti-proliferative property of clusterin in prostate cancer cells [J]. Life Sci,2002,72(1):11-21.
[34]Gutacker C, Klock G, Diel P, et al. Nerve growth factor and epidermal growth factor stimulate clusterin gene expression in PC12 cells [J]. Biochem J,1999,339(P3):759-66.
[35]Jenne DE, Tschopp J. Molecular structure and functional characterization of a human complement cytolysis inhibitor found in blood and seminal plasma:identity to sulfated glycoprotein 2, a constituent of rat testis fluid [J]. Proc Natl Acad Sci U S A,1989,86(18): 7123-7.
[36]Jenne DE, Lowin B, Peitsch MC, et al. Clusterin (complement lysis inhibitor)forms a high density lipoprotein complex with apolipoprotein A-I in human plasma [J]. J Biol Chem, 1991,266(17):11030-6.
[37]May PC. Sulfated glycoprotein-2:an emerging molecular marker for neurodegeneration [J]. Ann N Y Acad Sci,1993,679:235-44.
[38]Sylvester SR, Morales C, Oko R, et al. Localization of sulfated glycoprotein-2(clusterin)on spermatozoa and in the reproductive tract of the male rat [J]. Biol Reprod,1991,45(1): 195-207.
[39]Collard MW, Griswold MD. Biosynthesis and molecular cloning of sulfated glycoprotein 2 secreted by rat Sertoli cells [J]. Biochemistry,1987,26(12):3297-303.
[40]Atlas-White M, Murphy BF, Baker HW. Localisation of clusterin in normal human sperm by immunogold electron microscopy [J]. Pathology,2000,32(4):258-61.
[41]Hochgrebe TT, Humphreys D, Wilson MR, et al, A reexamination the role of clusterin as a complement regulator [J]. Exp Cell Res,1999,249(1):13-21.
[42]Murphy BF, Kirszbaum L, Walker ID, et al. SP-40,40, a newly identified norma human serum protein found in the SC5b-9 complex of complement and in the immune deposits in glomerulonephritis [J]. J Clin Invest,1988,81(6):1858-64.
[43]Danik M, Chabot JG, Mercier C, et al. Human gliomas and epileptic foci express high levels of a mRNA related to rat testicular sulfated glycoprotein 2, a purported marker of cell death [J]. Proc Natl Acad Sci U S A,1991,88(19):8577-81.
[44]Palmer DJ, Christie DL. Identification of molecular aggregates containing glycoproteins III, J, K (carboxypeptidase H) and H(Kex2-related proteases) in the soluble and membrane fractions of adrenal medullary chromaffin granules [J]. J Biol Chem,1992,267(28): 19806-12.
[45]Bartl MM, Luckenbach T, Bergner O, et al. Multiple receptors mediate apoJ-dependent clearance of cellular debris into nonprofessional phagocytes [J]. Exp Cell Res,2001,271(1): 130-41.
[46]Silkensen JR, Skubitz KM, Skubitz AP, et al. Clusterin promotes the aggregation and adhesion of renal porcine epithelial cells [J]. J Clin Invest,1995,96(6):2646-53.
[47]Fritz IB, Burdzy K, Setchell B, et al. Ram rete testis fluid contains a protein (clusterin) which influences cell-cell interactions in vitro [J]. Biol Reprod,1983,28(5):1173-88.
[48]Debure L, Vayssiere JL, Rincheval V, et al. Intracellula clusterin causes juxtanuclear aggregate formation and mitochondrial alteration [J]. J Cel Sci,2003,116(Pt 15):3109-21.
[49]Bettuzzi S, Scorcioni F, Astancolle S, et al. Clusterin(SGP-2) transient overexpression decreases proliferation rate of SV40-immortalized human prostate epithelial cells by slowing down cell cycle progression [J]. Oncogene,2002,21(27):4328-34.
[50]Scaltriti M, Santamaria A, Paciucci R, et al. Intracellular clusterin induces G2-M phase arrest and cell death in PC-3 prostate cancer cells [J]. Cancer Res,2004,64(17):6174-82.
[51]Matsuda A, Itoh Y, Koshikawa N, et al. Clusterin, an abundant serum factor, is a possible negative regulator of MT6-MMP/MMP-25 produced by neutrophils [J]. J Biol Chem,2003, 278(38):36350-7.
[52]Seiberg M, Marthinuss J. Clusterin expression within skin correlates with hair growth [J]. Dev Dyn,1995,202(3):294-301.
[53]Thomas-Salgar S, Millis AJ. Clusterin expression in differentiating smooth muscle cells [J]. J Biol Chem,1994,269(27):17879-85.
[54]Kirszbaum L, Sharpe JA, Murphy B, et al. Molecular cloning and characterization of the novel, human complement-associated protein, SP-40,40:a link between the complement and reproductive systems [J]. EMBO J,1989,8(3):711-8.
[55]Ghiggeri GM, Brusehi M, Candiano G, et al. DePletion of clusterin in renal diseases causing nephritic syndrome [J]. Kidney Int,2002,62(6):2184-94.
[56]Harr SD, Uint L, Hollister R, et al. Brain expression of apolipoproteins E, J, and A-1 in Alzheimer's disease [J]. J Neurochem,1996,66(6):2429-35.
[57]Gelissen IC, Hochgrebe T, Wilson MR, et al. Apolipoprotein J (clusterin) induces cholesterol export from macrophage-foam cells:a potential anti-atherogenic function? [J]. Biochem J, 1998,331 (Pt1):231-7.
[58]O'Bryan MK, Baker HWG, Saunders JR, et al. Human seminal clusterin (SP-40,40) [J]. J Clin Invest,1990,85(5):1477-86.
[59]Forni M, Zannoni A, Tamanini C, et al. Opposite regulation of clusterin and LH receptor in the swine corpus luteum during luteolysis [J]. Reprod Nutr Dev,2003,43(6):517-25.
[60]Bailey R, Griswold MD. Clusterin in the male reproductive system:localization and possible function [J]. Mol Cell Endocrinol,1999,151(1-2):17-23.
[61]Humphreys DT, Carver JA, Easterbrook-Smith SB, et al. Clusterin ha chaperone-like activity similar to that of small heat shock proteins [J]. J Biol Chem,1999,274(11):6875-81.
[62]Poon S, Rybchyn MS, Easterbrook-Smith SB, et al. Mildly acidic pH activates the extracellular molecular chaperone clusterin [J]. J Biol Chem,2002,18;277(42):39532-40.
[63]Lakins JN, Poon S, Easterbrook-Smith SB, et al. Evidence that clusterin has diserete chaperone and ligand binding sites [J]. Bioehemistry,2002,41(1):282-91.
[64]Wellmann A, Thieblemont C, Pittaluga S, et al. Detection of differentially expressed genes in lymphomas using cDNA arrays:identification of clusterin as a new diagnostic marker for anaplastic large-cell lymphomas [J]. Blood,2000,15; 96(2):398-404.
[65]Xin DQ, Zhu XH, Ai JK, et al. Prevention of cell death in LNCaP cells by overexpression of clusterin [J]. Beijing Da Xue Xue Bao,2004,36(2):154-58.
[66]Sklar GN, Eddy HA, Jacobs SC, et al. Combined antitumor effect of suramin plus irradiation in human prostate cancer cells:the role of apoptosis [J]. J Urol,1993,150(5 P1):1526-32.
[67]Warri AM, Huovinen RL, Laine AM, et al. Apoptosis in toremifene-induced growth inhibition of human breast cancer cells in vivo and in vitro [J]. J Natl Cancer Inst,1993,85(17): 1412-8.
[68]Koch-Brandt C, Morgans C. Clusterin:a role in cell survival in the face of apoptosis? [J]. Prog Mol Subcell Biol,1996,16:130-49.
[69]Trougakos IP, So A, Jansen B, et al. Silencing expression of the clusterin/apolipoprotein gene in human cancer cells using small interfering RNA induces spontaneous apoptosis, reduced growth ability, and cell sensitization to genotoxic and oxidative stress [J]. Cancer Res,2004, 64(5):1834-42.
[70]Redondo M, Tellez T, Roldan MJ, et al. Anticlusterin treatment of breast cancer cells increases chemotherapy-and tamoxifen-sensitivity and counteracts the inhibitory action of dexamethasone on chemotherapy-induced cytotoxicity [J]. Breast Cancer Res,2007, 9(6):R86.
[71]Trougakos IP, Gonos ES. Clusterin/apolipoprotein J in human aging and cancer [J]. Int J Biochem Cell Biol,2002,34(11):1430-48.
[72]Pucci S, Bonanno E, Pichiorri F, et al. Modulation of different clusterin isoforms in human colon tumorigenesis [J]. Oncogene,2004,23(13):2298-304.
[73]Yamada K, Hori Y, Hanaufsa N, et al. Clusterin is up-regulated in glomerular mesangial cells in complement-mediated injury [J]. Kidney Int,2001,59(1):137-46.
[74]Saunders JR, Aminian A, McRae JL, et al. Clusterin depletion enhances immune glomerular injury in the isolated perufsed kidney [J]. Kidney Int,1994,45(3):817-27.
[75]Sehlegel PN, Matthews GJ, Ciehon Z, et al. Clusterin Production in the obstructed rabbit kidney:correlations with loss of renal function [J]. J Am Soc Nephrol,1992,3(5):1163-71.
[76]Obermuller N, Gretz W, Woude FJ, et al. Differentiation and cell polarity during renal cyst formation in the Han:SPRD(cy/+)rat, a model for ADPKD [J]. Am J Physiol,1997,273(3 Pt 2):357-71.
[77]Choi-Miura NH, Oda T. Relationship between multifunctional protein "clusterin" and Alzheimer disease [J]. Neurobiol Aging,1996,17(5):717-22.
[78]McLaughlin L, Zhu G, Mistry M, et al. Apolipoprotein J/clusterin limits the severity of murine autoimmune myocarditis [J]. J Clin Invest,2000,106(9):1105-13.
[79]Moretti RM, Marelli MM, Mai S, et al. Clusterin Isoforms Differentially Affect Growth and Motility of Prostate Cells:Possible Implications in Prostate Tumorigenesis [J]. Cancer Res, 2007,67 (21):10325-33.
[80]Kruger S, Ola V, Fischer D, et al. Prognostic significance of clusterin immunoreactivity in breast cancer [J]. Neoplasma,2007,54(1):46-50.
[81]Shannan B, Seifert M, Leskov K, et al. Challenge and promise:roles for clusterin in pathogenesis, progression and therapy of cancer [J]. Cell Death Differ,2006,13 (1):12-9.
[1]Abnizova I, te Boekhorst R, Walter K, et al. Some statistical properties of regulatory DNA sequences and their use in predicting regulatory regions in the Drosophila genome:the fluffy-tail test [J]. BMC Bioinformatics,2005,6:1-9.
[2]Kimura K, Wakamatsu A, Suzuki Y, et al. Diversification of transcriptional modulation: Large-scale of human genes identification and characterization of putative alternative promoters [J]. Genome Res,2006,16(1):55-65.
[3]Schmitt-John T, Engels JW. Promoter constmctions for effieient seeretion expression in Streptomyces lividans [J]. APPI Mierobiol Bioteehnol,1992,36(4):493-98.
[4]Jocab P, Monod J. Genetic regulatory mechanisms in the synthesis of proteins. J Mol Biol, 1961,3:318-56.
[5]Wang Z, Huang J, Zhong J, et al. Molecular cloning, promoter analysis, SNP detection of Clusterin gene and their associations with mastitis in Chinese Holstein cows [J]. Mol Biol Rep,2012,39(3):2439-45.
[6]张利博。牛Nrampl基因5’端调控区的启动子功能和SNP分析[D]。吉林大学。2009。
[7]周磊。bLF基因部分序列的PCR-SSCP分析及其作为乳腺炎抗性分子标记的可行性研究[D]。南京农业大学,2006。
[8]张利军,蔡亚非,刘庆华,等。奶牛乳铁蛋白基因启动子区PCR-RFLP分析与乳房炎的相关性[J]。福建农林大学学报,2005,34(1)：84-91。
[9]李国华,张沅,孙东晓,等。奶牛乳铁蛋白基因5’侧翼区PCR-SSCP多态性分析[J]。遗传,2004,26(6)：827-30。
[10]王洪梅,孔振兴,王长法,等。奶牛乳铁蛋白基因5’侧翼区遗传多态性及其与乳腺炎关联性分析[J]。遗传,2009,31(4)：393-9。
[11]Kaminski S, Olenski K, Brym P, et al. Single nucleotide polymorphism in the promoter region of the lactoferrin gene and its associations with milk performance traits in polish Holstein-friesian cows [J]. Genetika,2006,42(8):111-20.
[12]Daly M, Ross P, Giblin L, et al. Polymorphisms within the lactoferrin gene promoter in various cattle breeds [J]. Anim Biotechnol,2006,17(1):33-42.
[13]Li GH, Zhang Y, Sun DX, et al. Study on the polymorphism of bovine lactoferrin gene and its relationship with mastitis [J]. Animal Biotechnol,2004,15(1):67-76.
[14]Hamalainen T, Poutanen M, Huhtaniemi I.Promoter function of different length of the murine luteinizing hormone recept or gene 5'-flanking region in transfected gonadal cells and in transgenic mice [J]. Endocrino logy,2001,142(6):2427-34.
[15]Ikram-ul-Haq, Ashraf H, Iqbal J, et al. Production of alpha amylase by Bacillus licheniformis using an economical medium [J]. Bioresource Technology,2003,87(1):57-61.
[16]Veloshinie G, Lise K. Evaluation of different formulations of Bacillus licheniformis in mango packs house trials [J]. Biological Control,2006,37:237-42.
[17]Elisa AM, Jacques BS. China flavour ester synthesis by a new esterase from Bacillus licheniformis [J]. Journal of Molecular Catalysis B:Enzymatic,2000,10:377-83.
[18]Pnar C, Tuncer H. Ozdamar.Mass flux balance-based model and metabolic pathway engineering analysis for serine alkaline protease synthesis by Bacillus licheniformis [J]. Enzyme and Microbial Technology,1999,24:621-35.
[19]Ritu S, Uwe T. Bomscheuer, et al. Synthesis of kyotorphin precursor by anorganic solvent-stable protease from Bacillus lichenifor mis RSP-09-37 [J]. Journal of Molecular Catalysis B:Enzymatic,2004,32:1-5.
[20]Chow LT, Gelinas RE, Broker TR, et al. An amazing sequence arrangement at the 5'nds of adenovirus 2 messenger RNA [J]. Cell,1977,12(1):1-8.
[21]Gilbert W. Why genes in pieces? [J]. Nature,1978,271(5645):501.
[22]Choi E, Kuehl M, Wall R. RNA splicing generates a variant light chain from an aberrantly rearranged kappa gene [J]. Nature,1980,286(5775):776-9.
[23]Kramer A. The structure and function of proteins involved in mammalian pre-mRNA splicing [J]. Annu Rev Biochem,1996,65:367-409.
[24]Black DL. Mechanisms of alternative pre-messenger RNA splicing [J]. Annu Rev Biochem, 2003,72:291-336.
[25]Surono A, Takeshima Y, Wibawa T, et al. Circular dystrophin RNAs consisting of exons that were skipped by alternative splicing [J]. Hum Mol Genet,1999,8(3):493-500.
[26]Shapiro MB, Senapathy P. RNA splice junctions of different classes of eukaryotes:sequence statistics and functional implications in gene expression [J]. Nucleic Acids Res,1987,15 (17):7155-74.
[27]Aebi M, Hornig H, Weissmann C.5'cleavage site in eukaryotic pre-mRNA splicing is determined by the overall 5'splice region, not by the conserved 5'GU [J]. Cell,1987,50(2): 237-46.
[28]Zhang W, Liu H, Han K, et al. Region-specific alternative splicing in the nervous system: implications for regulation by the RNA-binding protein NAPOR [J]. RNA,2002,8(5): 671-85.
[29]Nilsen TW. The spliceosome:no assembly required? [J]. Mol Cell,2002,9(1):8-9.
[30]Staley JP, Guthrie C. Mechanical devices of the spliceosome:motors, clocks, springs, and things [J]. Cell,1998,92(3):315-26.
[31]Brow DA. Allosteric cascade of spliceosome activation [J]. Annu Rev Genet,2002,36: 333-60.
[32]Das R, Zhou Z, Reed R. Functional association of U2 snRNP with the ATP-independent spliceosomal complex E [J]. Mol Cell,2000, (5):779-87.
[33]Nilsen TW. A parallel spliceosome [J]. Science,1996,273(5283):1813.
[34]Tsai RT, Fu RH, Yeh FL, et al. Spliceosome disassembly catalyzed by Prp43 and its associated components Ntrl and Ntr2 [J]. Genes Dev,2005,19(24):2991-3003.
[35]Ladd AN, Cooper TA. Finding signals that regulate alternative splicing in the post-genomic era [J]. Genome Biol,2002,3(11):0008.
[36]Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome [J]. Nature,2001,409 (6822):860-921.
[37]Soret J, Gabut M, Tazi J. SR proteins as potential targets for therapy [J]. Prog Mol Subcell Biol,2006,44:65-87.
[38]Simard MJ, Chabot B. SRp30c is a repressor of 3'splice site utilization [J]. Mol Cell Biol, 2002,22(12):4001-10.
[39]Caceres JF, Kornblihtt AR. Alternative splicing:multiple control mechanisms and involvement in human disease [J]. Trends Genet,2002,18(4):186-93.
[40]Li Y, Blencowe BJ. Distinct factor requirements for exonic splicing enhancer function and binding of U2AF to the polypyrimidine tract [J]. J Biol Chem,1999,274(49):35074-9.
[41]Cote J, Dupuis S, Jiang Z, et al. Caspase-2 pre-mRNA alternative splicing:Identification of an intronic element containing a decoy 3'acceptor site [J]. Proc Natl Acad Sci USA,2001, 98(3):938-43.
[42]Stamm S. Signals and their transduction pathways regulating alternative splicing:a new dimension of the human genome [J]. Hum Mol Genet,2002,11(20):2409-16.
[43]Smith CW, Valcarcel J. Alternative pre-mRNA splicing:the logic of combinatorial control [J]. Trends Biochem Sci,2000,25(8):381-8.
[44]Li B, Wachtel C, Miriami E, et al. Stop codons affect 5'splice site selection by surveillance of splicing [J]. Proc Natl Acad Sci USA,2002,99(8):5277-82.
[45]Goldstrohm AC, Greenleaf AL, Garcia-Blanco MA. Co-transcriptional splicing of pre-messenger RNAs:considerations for the mechanism of alternative splicing [J]. Gene,2001, 277(1-2):31-47.
[46]Fuller-Pace FV. DExD/H box RNA helicases:multifunctional proteins with important roles in transcriptional regulation [J]. Nucleic Acids Res,2006,34(15):4206-15.
[47]Konig H, Ponta H, Herrlich P. Coupling of signal transduction to alternative pre-mRNA splicing by a composite splice regulator [J]. EMBO J,1998,17(10):2904-13.
[48]Lynch KW, Weiss A. A model system for activation-induced alternative splicing of CD45 pre-mRNA in T cells implicates protein kinase C and Ras [J]. Mol Cell Biol,2000,20 (1): 70-80.
[49]Tacke R, Mauley JL. Determinants of SR protein specificity [J]. Curr Opin Cell Biol,1999, 11(3):358-62.
[50]McVety S, Li L, Gordon PH, et al. Disruption of an exon splicing enhancer in exon 3 of MLH1 is the cause of HNPCC in a Quebec family [J]. J Med Genet,2006,43(2):153-6.
[51]Kawase T, Akatsuka Y, Torikai H, et al. Alternative splicing due to an intronic SNP in HMSD generates a novel minor histocompatibility antigen [J]. Blood,2007,110(3): 1055-63.
[52]Douglas KB, Windels DC, Zhao J, et al. Complement receptor 2 polymorphisms associated with systemic lupus erythematosus modulate alternative splicing [J]. Genes Immun,2009, 10(5):457-69.
[53]Hirose Y, Chiba K, Karasugi T, et al. A functional polymorphism in THBS2 that affects alternative splicing and MMP binding is associated with lumbar-disc herniation [J]. Am J Hum Genet,2008,82(5):1122-9.
[54]Murani E, Ponsuksili S, Seyfert HM, et al. Dual effect of a single nucleotide polymorphism in the first intron of the porcine secreted phosphoprotein 1 gene:allele-specific binding of C/EBP beta and activation of aberrant splicing [J]. BMC Mol Biol,2009,21; 10:96.
[55]Carlini DB, Genut JE. Synonymous SNPs provide evidence for selective constraint on human exonic splicing enhancers [J]. J Mol Evol,2006,62(1):89-98.
[56]ElSharawy A, Manaster C, Teuber M, et al. SNPSplicer:systematic analysis of SNP-dependent splicing in genotyped cDNAs [J]. Hum Mutat,2006,27(11):1129-34.
[57]Zhang Y, Bertolino A, Fazio L, et al. Polymorphisms in human dopamine D2 receptor gene affect gene expression, splicing, and neuronal activity during working memory [J]. Proc Natl Acad Sci USA,2007,18; 104(51):20552-7.
[58]Harari A, Ooms M, Mulder LC, et al. Polymorphisms and splice variants influence the antiretroviral activity of human APOBEC3H [J]. J Virol,2009,83(1):295-303.
[59]Paris AJ, Snapir Z, Christopherson CD, et al. A polymorphism that delays fibrosis in hepatitis C promotes alternative splicing of AZIN1, reducing fibrogenesis [J]. Hepatology,2011, 54(6):2198-207.
[60]Guyon-Debast A, Lecureuil A, Bonhomme S, et al. A SNP associated with alternative splicing of RPT5b causes unequal redundancy between RPT5a and RPT5b among Arabidopsis thaliana natural variation [J]. BMC Plant Biol,2010 Aug 3; 10:158.
[61]Modrek B, Lee C. A genomic view of alternative splicing [J]. Nat Genet,2002,30(1):13-9.
[62]Graveley BR. Alternative splicing:increasing diversity in the proteomic world [J]. Trends Genet,2001,17(2):100-7.
[63]Black DL. Protein diversity from alternative splicing:a challenge for bioinformatics and post-genome biology [J]. Cell,2000,103(3):367-70.
[64]Grabowski PJ, Black DL. Alternative RNA splicing in the nervous system [J]. Prog Neurobiol, 2001,65(3):289-308.
[65]Cogan JD, Phillips JA, Schenkman SS, et al. Familial growth hormone deficiency:a model of dominant and recessive mutations affecting a monomeric protein [J]. J Clin Endocrinol Metab,1994,79(5):1261-5.
[66]Moseley CT, Mullis PE, Prince MA, et al. An exon splice enhancer mutation causes autosomal dominant GH deficiency [J]. J Clin Endocrinol Metab,2002,87(2):847-52.
[67]Zhou Z, Licklider LJ, Gygi SP, et al. Comprehensive proteomic analysis of the human spliceosome [J]. Nature,2002,12; 419(6903):182-5.
[68]Makarova OV, Makarov EM, Liu S, et al. Protein 61K, encoded by a gene (PRPF31) linked to autosomal dominant retinitis pigmentosa, is required for U4/U6*U5 tri-snRNP formation and pre-mRNA splicing [J]. EMBO J,2002,1;21(5):1148-57.
[69]Liquori CL, Ricker K, Moseley ML, et al. Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9 [J]. Science,2001,3; 293(5531):864-7.
[70]Savkur RS, Philips AV, Cooper TA. Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy [J]. Nat Genet,2001, 29(1):40-7.
[71]Charlet-B N, Savkur RS, Singh G, et al. Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing [J]. Mol Cell,2002,10(1): 45-53.
[72]Nissim-Rafinia M, Kerem B. Splicing regulation as a potential genetic modifier [J]. Trends Genet,2002,18(3):123-7.
[73]Sorek R, Basechess O, Safer HM. Computational analysis and experimental validation of tumor-associated alternative RNA splicing in human cancer [J]. Cancer Res,2003,63(20): 655-7.
[74]Sneath RJ, Mangham DC. The normal structure and function of CD44 and its role in neoplasia [J]. Mol Pathol,1998,51(4):191-200.
[75]Heider KH, Kuthan H, Stehle G, et al. CD44v6:a target for antibody-based cancer therapy [J]. Cancer Immunol Immunother,2004,53(7):567-79.
[76]Gargani M, Valentini A, Pariset L. A novel point mutation within the EDA gene causes an exon dropping in mature RNA in Holstein Friesian cattle breed affected by X-linked anhidrotic ectodermal dysplasia [J]. BMC Vet Res,2011,8; 7:35.
[77]王兴平,罗仍卓么,许尚忠,等。牛IRAK2基因有两种选择性剪接表达产物[J]。中国生物化学与分子生物学报,2009,25(3)：292-6。
[78]Huang JM, Wang ZY, Ju ZH, et al. Two splice variants of the bovine lactoferrin gene identified in Staphylococcus aureus isolated from mastitis in dairy cattle [J]. Genet Mol Res, 2011,21; 10(4):3199-203.
[79]Ju Z, Wang C, Li Q, et al. Alternative splicing and mRNA expression analysis of bovine SLAMF7 gene in healthy and mastitis mammary tissues [J]. Mol Biol Rep,2012,39(4): 4155-61.
[80]Hou Q, Huang J, Ju Z,et al. Identification of Splice Variants, Targeted MicroRNAs and Functional Single Nucleotide Polymorphisms of the BOLA-DQA2 Gene in Dairy Cattle [J]. DNA Cell Biol,2011,15.
[81]Wang Z, Huang J, Xia P,et al. Alternative splicing and expression of cattle clusterin gene in healthy and mastitis-infected mammary tissues [J]. J. Anim.Sci.Adv,2012,2(4).
[82]David PB. MicroRNAs:Genomics, biogenesis, mechanism and function [J]. Cell,2004, 116(2):281-297.
[83]Hutvagner G, Zamore PD. A microRNA in a multi-ple-turnover RNAi enzyme complex [J]. Science,2002,297(5589):2056-60.
[84]Zeng Y, Yi R, Cullen BR. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci USA [J].2003,100(17):9779-84.
[85]Doench JG, Peterson CP, Sharp PA. siRNAs can function as miRNAs [J]. Genes & Development,2003,17(4):438-42.
[86]Chen F, Yin QW. MiRNAs regulate the gene expression [J]. Chinese Science Bulletin,2005, 50(13):1289-99.
[87]Ambros V, Bartel B, Bartel DP, et al. A uniform system for microRNA annotation [J]. RNA, 2003,9(3):277-9.
[88]Berezikov E, Cuppen E, Plasterk RH. Approaches to mi-croRNA discovery [J]. Nature Genetics,2006,38:2-7.
[89]Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 [J]. Cell,1993,75(5):843-54.
[90]Reinhart BJ, Slack FJ, Basson M, et al. The 21 nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans [J]. Nature,2000,403(6772):901-6.
[91]Johnston RJ, Hobert O. A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans [J]. Nature,2003,426(6968):845-9.
[92]Chang S, Johnston RJ Jr, Frokjaer-Jensen C, et al. MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode [J]. Nature,2004, 430(7001):785-9.
[93]Krichevsky AM, King KS, Donahue CP, et al. A microRNA array reveals extensive regulation of microRNAs during brain development [J]. RNA,2004,10(3):551:1274-81.
[94]Xu P, Vernooy SY, Guo M, et al. The Drosophila microRNA mir-14 suppresses cell death and is required for normal fat metabolism [J]. Current Biology,2003,13(9):790-5.
[95]Clop A, Marcq F, Takeda H, et al. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep [J]. Nature Genetics,2006, 38(7):813-8.
[96]Michael MZ, O'Connor SM, van Ho1st Pellekaan NG, et al. Reduced accumulation of specific microRNAs in colorectal neoplasia [J]. Mol Cancer Res,2003,1(12):882-91.
[97]Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13ql4 in chronic lymphocytic leukemia [J]. Proc Natl Acad Sci USA,2002,99(24):15524-9.
[98]Takamizawa J, Konishi H, Yanagisawa K, et al. Reduced expressionof the let-7 microRNAs in human lung cancers in association with shortened postoperative survival [J]. Cancer Research,2004,64 (11):3753-6.
[99]Volinia S, Calin GA, Liu CG, et al. A microRNA expression signature of human solid tumors defines cancer gene targets [J]. PNAS,2006,103(7):2257-61.
[100]Taganov KD, Boldin MP, Chang KJ, et al. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses [J]. Proc Natl Acad Sci USA.2006,15; 103(33):12481-6.
[101]Wu H, Neilson JR, Kumar P, et al. miRNA profiling of nai've, effector and memory CD8 T cells [J]. PLoS One,2007,10; 2(10):e1020.
[102]Sonkoly E, Pivarcsi A. Advances in microRNAs:implications for immunity and inflammatory diseases [J]. J Cell Mol Med,2009,13(1):24-38.
[103]Hata T, Murakami K, Nakatani H, et al. Isolation of bovine milk-derived microvesicles carrying mRNAs and microRNAs [J]. Biochem Biophys Res Commun,2010,28; 396(2): 528-33.
[104]Kosaka N, Izumi H, Sekine K, et al. microRNA as a new immune-regulatory agent in breast milk [J]. Silence,2010,1; 1(1):7.
[105]Zhou Q, Li M, Wang X, et al. Immune-related microRNAs are abundant in breast milk exosomes [J]. Int J Biol Sci,2012,8(1):118-23.
[106]Chen X, Gao C, Li H, et al. Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products [J]. Cell Res,2010,20(10):1128-37.
[107]Coutinho LL, Matukumalli LK, Sonstegard TS, et al. Discovery and profiling of bovine microRNAs from immune-related and embryonic tissues [J]. Physiol Genomics,2007,14; 29(1):35-43.
[108]Gu Z, Eleswarapu S, Jiang H. Identification and characterization of microRNAs from the bovine adipose tissue and mammary gland [J]. FEBS Lett,2007,6; 581(5):981-8.
[109]Feuermann Y, Robinson GW, Zhu BM, et al. The miR-17/92 cluster is targeted by STAT5 but dispensable for mammary development [J]. Genesis,2012,2:10.1002.
[110]Hata T, Murakami K, Nakatani H, et al. Isolation of Bovine Milk-Derived Microvesicles Carrying mRNAs and microRNAs [J]. Biochem Biophys Res Commun,2010,396:528-33.
[111]李惠侠,王振云,张震,等。高温条件下miRNA-24对奶牛乳腺上皮细胞增殖与凋亡的影响[J]。中国农业科学,2010,43(22)：4732-38。
[112]万中英,佟慧丽,李庆章,等。中药王不留行增乳活性单体及催乳素对奶牛乳腺上皮细胞特异性miRNA的影响[J]。中国畜牧兽医,2010,37(8)：230-2。
[113]Jiang S, Zhang HW, Lu MH, et al. MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene [J]. Cancer Res,2010,70(8): 3119-27.
[114]Li H, Bian C, Liao L, et al. miR-17-5p promotes human breast cancer cell migration and invasion through suppression of HBP1 [J]. Breast Cancer Res Treat,2011,126(3):565-75.
[115]Wright JA, Richer JK, Goodall GJ. MicroRNAs and EMT in mammary cells and breast cancer [J]. J Mammary Gland Biol Neoplasia,2010,15(2):213-23.
[116]Tavazoie SF, Alarcon C, Oskarssoon T, et al. Endogenous human microRNAs that suppress breast cancer metastasis [J]. Nature,2008,451(7175):147-52.
[117]Sempere LF, Christensen M, Silahtaroglu A, et al. Altered microRNA expression confined to specific epithelial cell subpopulations in breast cancer [J]. Cancer Res,2007,67(24): 11612-20.
[118]Horikawa Y, Wood CG, Yang HS, et al. Single nucleotide polymorphisms of microRNA machinery genes modify the risk of renal cell carcinoma [J]. Clin Cancer Res,2008,14(23): 7956-62.
[119]Yang HS, Dinney CP, Ye YQ,et al. Evaluation of genetic variants in microRNA-related genes and risk of bladder cancer [J]. Cancer Res,2008,68(7):2530-7.
[120]Gottwein E, Cai XZ, Cullen BR. A novel assay for viral microRNA function identifies a single nucleotide polymorphism that affects Drosha processing [J]. J Virol,2006,80(11): 5321-6.
[121]Duan RH, Pak CH, Jin P. Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA [J]. Hum Mol Genet,2007,16(9):1124-31.
[122]Mencia A, Modamio-Hoybjor S, Redshaw N, et al. Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss [J]. Nat Genet,2009, 41(5):609-13.
[123]Li W, Duan R, Kooy F, et al.Germline mutation of microRNA-125a is associated with breast cancer [J]. J Med Genet,2009,46(5):358-60.
[124]Kontorovich T, Levy A, Korostishevsky M,et al. Single nucleotide polymorphisms in miRNA binding sites and miRNA genes as breast/ovarian cancer risk modifiers in Jewish high-risk women [J]. Int J Cancer,2010,127(3):589-97.
[125]Iorio MV, Visone R, Dileva G, et al. MicroRNA signatures in human ovarian cancer [J]. Cancer Res,2007,67(18):8699-707.
[126]Bandres E, Agirre X, Bitarte N, et al. Epigenetic regulation of microRNA expression in colorectal cancer [J]. Int J Cancer,2009,125(11):2737-43.
[127]Chayka O, Corvetta D, Dews M, et al. Clusterin, a haploinsufficient tumor suppressor gene in neuroblastomas [J]. J Natl Cancer Inst,2009,6; 101(9):663-7.
[128]Figure 2-lto 2-6. Molecular Biology of the Gene.
[1]Zhang CK, Lin W, Cai YN, et al. Characterization of the genomic structure and tissue-specific promoter of the human nuclear receptor NR5A2 (hB1F) gene [J]. Gene,2001,8; 273 (2): 239-49.
[2]Makova KD, Ramsay M, Jenkins T, et al. Human DNA sequence variation in a 6.6-kb region containing the melanocortin 1 receptor promoter [J]. Genetics,2001,158 (3):1253-68.
[3]Nott A, Meislin SH, Moore MJ.A quantitative analysis of intron effects on mammalian gene expression [J]. RNA,RNA,2003,9(5):607-17.
[4]Zan LS, Zhang JL, Liu XW. Association study on AGPAT6 intron3 polym-orphism and milk performance of dairy cattle [J].Scientia Agricultura Sinica,2007,40(7):1498-1503.
[5]Ando Z, Sato S, Ikeda K, et al. Slc12a2 is a direct target of two closely related homeobox proteins, Sixl and Six4 [J]. FFBS J,2005,272(12):3026-41.
[6]Kumar JP. The sine oculis homeobox (SIX) family of transcription factors as regulators of development and disease [J]. Cell Mol Life Sci,2009,66(4):565-83.
[7]Hariri AR, Mattay VS, Tessitore A et al. Serotonin transporter genetic variation and the response of the human amygdale [J]. Science,2002,19,297 (5580):400-3.
[8]Kitamura A, Hasegawa G, Obayashi H, et al. Interleukin-6 polymorphism (-634C/G) in the promotor region and the progression of diabetic nephropathy in type 2 diabetes [J]. Diabet Med,2002,19 (12):1000-5.
[9]Fallin D, Cohen A, Essioux L, et al. Genetic analysis of case/control data using estimated haplotype frequencies:application to APOE locus variation and Alzheimer's disease [J]. Genome Res,2001,11(1):143-151.
[10]Liu W, Wang J, Li Q, et al. Correlation analysis between three novel SNPs of the Src gene in bovine and milk production traits [J]. Mol Biol Rep,2010,37(8):3771-7.
[11]Wang Z, Wang G, Huang J, et al. Novel SNPs in the ATP1B2 gene and their associations with milk yield, milk composition and heat-resistance traits in Chinese Holstein cows [J]. Mol Biol Rep,2011,38(3):1749-55.
[1]Abnizova I, Boekhorst R, Walter K, et al. Some statistical properties of regulatory DNA sequences and their use in predicting regulatory regions in the Drosophila genome:the fluffy-tail test [J]. BMC Bioinformatics,2005,27(6):109.
[2]L i D, Firozi PF, Wang LE, et al. Sensitivity to DNA damage induced by benzo (a) pyrene diol epoxide and risk of lung cancer:a case-control analysis [J]. Cancer Res,2001,61(4): 1445-50.
[3]Xuan Z, Zhao F, Wang J, et al. Genome-wide promoter extraction and analysisin human, mouse and rat. Genome Biol [J].2005,6(8):R72.
[4]Purrello M, Bettuzzi S, Di Pietro C, et al. The gene for SP-40,40, human homolog of rat sulfated glycoprotein 2, rat clusterin, and rat testosterone-repressed prostate message 2, maps to chromosome 8 [J]. Genomics,1991,10(1):151-6.
[5]Michel D, Chatelain G, North S, et al. Stress-induced transcription of the clusterin/apoJ gene [J]. Biochem J,1997,328:45-50.
[6]刘召华,郭洪年,郑光宇,等。ACA基因启动子的克隆及功能初探[J].生物工程学报。2005,25(1)：139-143。
[7]杨咏梅,曹英林,梁晓红,等。hTERT启动子调控的TRAIL基因载体的构建及表达[J].山东大学学报(医学版),2005,1：22-26.
[8]Hamalainen T, Poutanen M, Huhtaniemi I. Promoter function of different length of the murine luteinizing hormone recept or gene 5'2flanking region in transfected gonadal cells and in transgenic mice [J]. Endocrino logy,2001,142(6):2427-34.
[9]JACOB F, MONOD J. Genetic regulatory mechanisms in the synthesis of proteins [J]. J Mol Biol,1961,3:318-56.
[1]Matlin AJ, Clark F, Smith CW. Understanding alternative splicing:towards a cellular code [J]. Nat Rev Mol Cell Biol,6(5):386-98.
[2]Srebrow A, Komblihtt AR. The connection between splicing and cancer [J]. J Cell Sci,2006, 119(13):2635-41.
[3]Chacko E, Ranganathan S.Genome-wide analysis of alternative splicing in cow:implications in bovine as a model for human diseases [J]. BMC Genomics,2009,10(3):S11.
[4]Caceres JF, Komblihtt AR. Alternative Splicing:multiple control mechanisms and involvement in human disease [J]. Trends Genet,18(4):186-93.
[5]Jones SE, Jomary C. Clusterin [J]. Int J Biochem Cell Biol.2002,34(5):427-31.
[6]Swanson KM, Stelwagen K, Dobson J, et al. Transcriptome profiling of Streptococcus uberis-induced mastitis reveals fundamental differences between immune gene expression in the mammary gland and in a primary cell culture model [J]. J Dairy Sci.2009,92(1):117-29.
[7]French LE, Wohlwend A, Sappino AP, et al. Human clusterin gene expression is confined to surviving cells during in vitro programmed cell death [J]. J Clin Invest,1994,93(2):877-84.
[8]Yang CR, Leskov K, Hosley-Eberlein K, et al. Nuclear clusterin/XIP8, an x-ray-induced Ku70-binding protein that signals cell death [J]. Proc Natl Acad Sci USA,2000,97(11): 5907-12.
[1]Carrington JC, Ambros V. Role of microRNAs in plant and animal development [J]. Science, 2003,301(5631):336-8.
[2]Bartel DP. MicroRNAs:Genomics, Biogenesis, Mechanism, and Function [J]. Cell,2004,23; 116(2):281-97
[3]Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation:MicroRNAs can up-regulate translation [J]. Science.2007,21; 318(5858):1931-4.
[4]Fang Z, Rajewsky N. The impact of miRNA target sites in coding sequences and in 3'UTRs [J]. PLoS One,2011,22; 6(3):e18067.
[5]Liao Y, Du X, Lonnerdal B. miR-214 regulates lactoferrin expression and pro-apoptotic function in mammary epithelial cells [J]. J Nutr,2010,140(9):1552-6.
[6]Ambros V, Bartel B, Bartel DP, et al. A uniform system for microRNA annotation [J]. RNA, 2003,9(3):277-9.
[7]Berezikov E, Cuppen E, Plasterk RH. Approaches to microRNA discovery [J]. Nature Genetics,2006,38:S2-S7.
[8]Chayka O, Corvetta D, Dews M, et al. Clusterin, a haploinsufficient tumor suppressor gene in neuroblastomas [J]. J Natl Cancer Inst,2009,6;101(9):663-77.
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