辅助性原位部分肝移植治疗肝豆状核变性的实验研究
|
摘要
第一部分实验一小鼠原位肝移植模型的建立
目的探讨小鼠原位肝移植模型技术的改进,为深入进行移植免疫、肝再生及缺血再灌注损伤等研究提供动物模型平台。方法按“双袖套”法完成小鼠原位肝移植模型50台,对供者手术、袖套安装及受者肝上下腔静脉吻合等方法进行技术改进,总结手术技巧,并评估手术时间、手术成功率及长期存活率。结果供者手术时间、受者无肝期时间及受者手术时间分别为(18±2)min、(17±2)min、(43±3) min。手术成功率为92%,100d存活率为85%。结论该方法可快速获取高质量供肝,同时无肝期的缩短可保证较高的手术成功率。
第一部分实验二小鼠辅助性原位部分肝移植模型的建立目的探讨建立小鼠辅助性原位部分肝移植模型的技术方法,进一步为临床该术式的开展提供小动物的实验数据支持。方法完成小鼠辅助性原位部分肝移植模型50台,门静脉采用袖套法吻合,肝静脉采用端端丝线吻合,胆道采用支架胆肠吻合,总结手术技巧,并评估手术时间、手术成功率及长期存活率。结果供者手术时间、受者无肝期时间及受者手术时间分别为(30±3)min、(6±1)min、(58±5) min。手术成功率为96%,术后4w存活率为88%。结论该方法技术可靠,成功率高,可为辅助性原位部分肝移植的基础研究提供帮助。
第二部分实验一Atp7b-/-小鼠的繁育、基因型鉴定及铜代谢特点分析
目的探讨Atp7b-/-小鼠的繁育、基因型鉴定及铜代谢特点,进一步研究ATP7B基因对铜代谢的影响。方法繁育采取杂合子配种的方法,PCR鉴定子代基因型,铜含量采用原子吸收光谱法检测,并行HE染色检查组织病理学改变。结果基因型鉴定结果符合孟德尔规律,Atp7b-/-.小鼠肝铜一直处于较高的水平,为野生型对照的25倍以上；血清铜水平在20周龄达到高峰,约为同龄野生型对照的两倍,且20周龄几乎所有的Atp7b-/-.小鼠肝脏均出现炎症坏死、纤维化及再生结节形成。结论Atp7b-/-小鼠基因型遗传稳定,肝脏病理改变明显,是理想的模拟肝豆状核变性肝脏病变的动物模型。
第二部分实验二辅助性原位部分肝移植治疗肝豆状核变性的实验研究
目的探讨辅助性原位部分肝移植对肝豆状核变性小鼠的治疗效果。方法利用Atp7b-/-小鼠为受体,Atp7b+/+小鼠为供体,分8和20周龄两个时间点行左外叶辅助性原位部分肝移植,移植肝体积约为受体肝的38%,观察移植术后生存率,比较铜代谢和肝功能的相关指标的变化。结果8和20周龄时间点移植术后生存率分别为,术后血清铜、自身肝铜、血清铜蓝蛋白活性及肝功能指标均有改善,其中8周龄移植术后肾铜和脑铜水平较对照明显降低,自身肝的组织病理改变明显轻于对照；20周龄移植术后供肝明显增生,自身病肝萎缩,且更小体积的移植肝(约为受体肝的19%)也能纠正铜代谢的紊乱,能达到全肝移植效果,但较后者手术风险更低。结论左外叶辅助性原位部分肝移植可以替代全肝移植治疗肝豆状核变性,同时早期移植可以延缓肝脏病变的进程,减少铜在其他组织器官中的沉积,但具体最低多少体积肝脏可以满足机体铜代谢需要,有待进一步研究。
PartⅠExperimentⅠEstablishment of orthotopic liver transplantation in mice
Objective To improve the technique of orthotopic liver transplantation model in mice and build animal model on the study of transplantation immunity, liver regeneration and ischemical reperfusion injury.
Methods According to "two-cuff" method,the surgical technic of harvesting donor's liver,fixing the cuff and the anastomosis of superior and inferior caval vein were improved.
Results The operation time of harvesting donor's liver and anhepatic phase and recipient were (18±2) min, (17±2) min and (43±3) min.The model success rate was 92%,and the 100-day survival was 85%.
Conclusions High quality liver could be harvested by this improved method,and short anhepatic phase ensured the high model success rate.
Part I Experiment II Establishment of auxiliary partial
orthotopic liver transplantation in miceObjective To explore the technique of auxiliary partial orthotopic livertransplantation model in mice and provied experimental animal data for clinicalapplication.
Methods The donor portal vein and hepatic vein are anastomosed with Cuff andsutrue technique respectively. The donor bile duct is implanted into recipientduodenum.
Results The operation time of harvesting donors liver and anhepatic phase andrecipient were (30士3) min, (6士1) min and (58士5) min. The model successrate was 96 %,and the 4-week survival was 88 %.Conclusions The animal model was stable with high success-rate and can be used forthe study of auxiliary partial orthotopic liver transplantation.
Part II Experiment I Reproduction and genotypeidentilfcation of Atp7b-/- mouse and its disorder of copper metabolism
Objective To explore the reproduction and genotype identification of Atp7b-/- mouseand its disorder of copper metabolism.
Methods The heterozygous mice were used for breeding, and the genotypeidentification of offspring was used by PCR. Copper contents were determined byatomic absorption spectrometry and HE staining was made for examination ofhistopathological change.
Results The analysis of genotype indentification fit the Mendel's laws. HepaticAcopper of Atp7b-/- mice were about 25 times more than wildtype, but serum copperincreased and peaked at 20 week old and were twice more than wildtype. At 20 weekold, hepatocellular necrosis, fibrosis and nodules were detected in almost all theAtp7b-/- mice. Conclusions The Atp7b-/- mice could be inherited stably, and their had significant hepatic histopathological change that can be an ideal experimental animal of Wilson's disease.
PartⅡExperimentⅡExperimental study on auxiliary partial orthotopic liver transplantation for Wilson's disease
Objective To evaluate the treatment effectiveness of auxiliary partial orthotopic liver transplantation for Wilson's disease.
Methods Auxiliary partial orthotopic liver transplantations were performed at 8 and 20 weeks old and the Left lateral lobe was the donor liver which accounts for 38% of the total recipient liver. Atp7b-/- mice were recipients, and Atp7b+/+ mice were donors. The survival and index of copper metabolism and liver function were observed after operation.
Results The postoperative survival of 8 and 20 weeks time point were 92% and 85% respectively. Serum copper, remanent liver copper, serum ceruloplasmin activity and liver function were improved postoperatively, and in 8 weeks time point kidney copper and brain copper content decreased after operation, meanwhile the pathological changes of remanent liver was slighter than control; in 20 weeks time point, the donor liver proliferated and the remanent liver atrophied after operation, and the smaller donor liver (19% of total recipient liver) could also corrected the disorder of copper metabolism as same as OLT, but had lower surgical risk.
Conclusions Left lateral lobe auxiliary partial orthotopic liver transplantation could take the place of orthotopic total liver transplantation for Wilson's disease, and early transplantation performed, the pathological process of remanent liver delayed and copper deposition in other ograns decreased. However, the minimum volume of liver meet the body's copper metabolic needs still needed to be further studied.
目的探讨小鼠原位肝移植模型技术的改进,为深入进行移植免疫、肝再生及缺血再灌注损伤等研究提供动物模型平台。方法按“双袖套”法完成小鼠原位肝移植模型50台,对供者手术、袖套安装及受者肝上下腔静脉吻合等方法进行技术改进,总结手术技巧,并评估手术时间、手术成功率及长期存活率。结果供者手术时间、受者无肝期时间及受者手术时间分别为(18±2)min、(17±2)min、(43±3) min。手术成功率为92%,100d存活率为85%。结论该方法可快速获取高质量供肝,同时无肝期的缩短可保证较高的手术成功率。
第一部分实验二小鼠辅助性原位部分肝移植模型的建立目的探讨建立小鼠辅助性原位部分肝移植模型的技术方法,进一步为临床该术式的开展提供小动物的实验数据支持。方法完成小鼠辅助性原位部分肝移植模型50台,门静脉采用袖套法吻合,肝静脉采用端端丝线吻合,胆道采用支架胆肠吻合,总结手术技巧,并评估手术时间、手术成功率及长期存活率。结果供者手术时间、受者无肝期时间及受者手术时间分别为(30±3)min、(6±1)min、(58±5) min。手术成功率为96%,术后4w存活率为88%。结论该方法技术可靠,成功率高,可为辅助性原位部分肝移植的基础研究提供帮助。
第二部分实验一Atp7b-/-小鼠的繁育、基因型鉴定及铜代谢特点分析
目的探讨Atp7b-/-小鼠的繁育、基因型鉴定及铜代谢特点,进一步研究ATP7B基因对铜代谢的影响。方法繁育采取杂合子配种的方法,PCR鉴定子代基因型,铜含量采用原子吸收光谱法检测,并行HE染色检查组织病理学改变。结果基因型鉴定结果符合孟德尔规律,Atp7b-/-.小鼠肝铜一直处于较高的水平,为野生型对照的25倍以上；血清铜水平在20周龄达到高峰,约为同龄野生型对照的两倍,且20周龄几乎所有的Atp7b-/-.小鼠肝脏均出现炎症坏死、纤维化及再生结节形成。结论Atp7b-/-小鼠基因型遗传稳定,肝脏病理改变明显,是理想的模拟肝豆状核变性肝脏病变的动物模型。
第二部分实验二辅助性原位部分肝移植治疗肝豆状核变性的实验研究
目的探讨辅助性原位部分肝移植对肝豆状核变性小鼠的治疗效果。方法利用Atp7b-/-小鼠为受体,Atp7b+/+小鼠为供体,分8和20周龄两个时间点行左外叶辅助性原位部分肝移植,移植肝体积约为受体肝的38%,观察移植术后生存率,比较铜代谢和肝功能的相关指标的变化。结果8和20周龄时间点移植术后生存率分别为,术后血清铜、自身肝铜、血清铜蓝蛋白活性及肝功能指标均有改善,其中8周龄移植术后肾铜和脑铜水平较对照明显降低,自身肝的组织病理改变明显轻于对照；20周龄移植术后供肝明显增生,自身病肝萎缩,且更小体积的移植肝(约为受体肝的19%)也能纠正铜代谢的紊乱,能达到全肝移植效果,但较后者手术风险更低。结论左外叶辅助性原位部分肝移植可以替代全肝移植治疗肝豆状核变性,同时早期移植可以延缓肝脏病变的进程,减少铜在其他组织器官中的沉积,但具体最低多少体积肝脏可以满足机体铜代谢需要,有待进一步研究。
PartⅠExperimentⅠEstablishment of orthotopic liver transplantation in mice
Objective To improve the technique of orthotopic liver transplantation model in mice and build animal model on the study of transplantation immunity, liver regeneration and ischemical reperfusion injury.
Methods According to "two-cuff" method,the surgical technic of harvesting donor's liver,fixing the cuff and the anastomosis of superior and inferior caval vein were improved.
Results The operation time of harvesting donor's liver and anhepatic phase and recipient were (18±2) min, (17±2) min and (43±3) min.The model success rate was 92%,and the 100-day survival was 85%.
Conclusions High quality liver could be harvested by this improved method,and short anhepatic phase ensured the high model success rate.
Part I Experiment II Establishment of auxiliary partial
orthotopic liver transplantation in miceObjective To explore the technique of auxiliary partial orthotopic livertransplantation model in mice and provied experimental animal data for clinicalapplication.
Methods The donor portal vein and hepatic vein are anastomosed with Cuff andsutrue technique respectively. The donor bile duct is implanted into recipientduodenum.
Results The operation time of harvesting donors liver and anhepatic phase andrecipient were (30士3) min, (6士1) min and (58士5) min. The model successrate was 96 %,and the 4-week survival was 88 %.Conclusions The animal model was stable with high success-rate and can be used forthe study of auxiliary partial orthotopic liver transplantation.
Part II Experiment I Reproduction and genotypeidentilfcation of Atp7b-/- mouse and its disorder of copper metabolism
Objective To explore the reproduction and genotype identification of Atp7b-/- mouseand its disorder of copper metabolism.
Methods The heterozygous mice were used for breeding, and the genotypeidentification of offspring was used by PCR. Copper contents were determined byatomic absorption spectrometry and HE staining was made for examination ofhistopathological change.
Results The analysis of genotype indentification fit the Mendel's laws. HepaticAcopper of Atp7b-/- mice were about 25 times more than wildtype, but serum copperincreased and peaked at 20 week old and were twice more than wildtype. At 20 weekold, hepatocellular necrosis, fibrosis and nodules were detected in almost all theAtp7b-/- mice. Conclusions The Atp7b-/- mice could be inherited stably, and their had significant hepatic histopathological change that can be an ideal experimental animal of Wilson's disease.
PartⅡExperimentⅡExperimental study on auxiliary partial orthotopic liver transplantation for Wilson's disease
Objective To evaluate the treatment effectiveness of auxiliary partial orthotopic liver transplantation for Wilson's disease.
Methods Auxiliary partial orthotopic liver transplantations were performed at 8 and 20 weeks old and the Left lateral lobe was the donor liver which accounts for 38% of the total recipient liver. Atp7b-/- mice were recipients, and Atp7b+/+ mice were donors. The survival and index of copper metabolism and liver function were observed after operation.
Results The postoperative survival of 8 and 20 weeks time point were 92% and 85% respectively. Serum copper, remanent liver copper, serum ceruloplasmin activity and liver function were improved postoperatively, and in 8 weeks time point kidney copper and brain copper content decreased after operation, meanwhile the pathological changes of remanent liver was slighter than control; in 20 weeks time point, the donor liver proliferated and the remanent liver atrophied after operation, and the smaller donor liver (19% of total recipient liver) could also corrected the disorder of copper metabolism as same as OLT, but had lower surgical risk.
Conclusions Left lateral lobe auxiliary partial orthotopic liver transplantation could take the place of orthotopic total liver transplantation for Wilson's disease, and early transplantation performed, the pathological process of remanent liver delayed and copper deposition in other ograns decreased. However, the minimum volume of liver meet the body's copper metabolic needs still needed to be further studied.
引文
[1]、Kamada N,Calne RY.Orthotopic liver transplantation in the rat. Technique using cuff for portal vein anastomosis and biliary drainage[J]. Transplantation, 1979,28:47-50.
[2]、Qian SG,Fung JJ.Demetris AV,et al.Orthotopic liver transplantation in the mouse[J]. Transplantation,1991,52:562-564.
[3]、He SQ, Atkinson C, Qiao F et al. Ketamine-Xylazine-Acepromazine compared with isoflurane for anesthesia during liver transplantation in rodents [J]. J Am Assoc Lab Anim Sci,2010,49(1):45-51.
[4]、Huang DR,Wu ZJ,Zhu Y.Modified arterialization of orthotopic liver transplantation in a mouse model[J]. Hepatobiliary Pancreat Dis Int,2010,9:264-268.
[5]、Qian S,Fung JJ,Demetris AJ,et al.Allogeneic orthotopic liver transplantation in mice:a preliminary study of rejection across well-defined MHC barriers[J]. Transplant Proc,1991,23:705-706.
[6]、Morita M, Fujino M, Jiang G, et al. PD-1/B7-H1 interaction contribute to the spontaneous acceptance of mouse liver allograft[J]. Am J Transplant,2010,10:40-46.
[1]. Terpstra OT, Schalm SW, Weimar W, et al. Auxiliary partial liver transplantation for end-stage chronic liver disease[J]. N Engl J Med,1988,319(23):1507-1511.
[2]. Gubernatis G, Pichlmayr R, Kemnitz J, et al. Auxiliary partial orthotopic liver transplantation (APOLT) for fulminant hepatic failure:first successful case report[J]. World J Surg,1991,15(5):660-665;discussion 665-666.
[3]. Chen XP An experimental study of auxiliary partial liver allotransplantation in dogs[J]. J Tongji Med Univ,1987,7(1):15-20.
[4]. Park YK, Kim BW, Wang HJ, et al. Auxiliary partial orthotopic living donor liver transplantation in a patient with Wilson's disease:a case report[J]. Transplant Proc, 2008,40(10):3808-3809.
[5]. Faraj W, Dar F, Bartlett A, et al. Auxiliary liver transplantation for acute liver failure in children[J].Ann Surg,2010,251(2):351-356.
[6]. Kobayashi T, Sato Y, Yamamoto S, et al. Auxiliary partial orthotopic living donor liver transplantation for fulminant hepatic failure with flat electroencephalogram:a case report[J].Transplant Proc,2010,42(3):990-993.
[7]. Ko S, Tanaka I, Kanokogi H, et al. Efficacy of auxiliary partial orthotopic liver transplantation for cure of hemophilia in a canine hemophilia A model[J]. Transplant Proc,2005,37(2):1131-1133.
[8]. Fukueda M, Ishizaki N, Hamada N, et al. Porcine model of auxiliary partial orthotopic liver transplantation for acute liver failure[J]. Transplantation, 2006,82(10):1312-1318.
[9]. Peng CH, Shi LB, Zhang HW, et al. Establishment of a new pig model for auxiliary partial orthotopic liver transplantation[J]. World J Gastroenterol, 2005,11 (6):917-921.
[10]. Palmes D, Diet1 KH, Drews G, et al. Auxiliary partial orthotopic liver transplantation:treatment of acute liver failure in a new rat model[J]. Langenbecks Arch Surg,2002,386(7):534-541.
[11]. Ikegami T, Nishizaki T, Yanaga K, et al. A novel auxiliary partial orthotopic liver transplantation model in rats[J]. Eur Surg Res,2000,32(5):267-273.
[12]. Kamada N and Calne RY Orthotopic liver transplantation in the rat. Technique using cuff for portal vein anastomosis and biliary drainage[J]. Transplantation, 1979,28(1):47-50.
[13]. Kobayashi T, Sato Y, Yamamoto S, et al. Feasibility of auxiliary partial living donor liver transplantation for fulminant hepatic failure as an aid for small-for-size graft:single center experience [J]. Transplant Proc,2009,41(1):262-264.
[14]. Matsuura T, Soejima Y and Taguchi T Auxiliary partial orthotopic living donor liver transplantation with a small-for-size graft for congenital absence of the portal vein[J]. Liver Transpl,2010,16(12):1437-1439.
[15]. Bismuth H, Azoulay D, Samuel D, et al. Auxiliary partial orthotopic liver transplantation for fulminant hepatitis. The Paul Brousse experience [J]. Ann Surg, 1996,224(6):712-724; discussion 724-716.
[16]. Hasegawa K, Sugawara Y and Makuuchi M Which is better to overcome the portal steal phenomenon in auxiliary partial orthotopic liver transplantation:inflow or outflow occlusion?[J]. Liver Transpl,2006,12(4):692-693.
[17]. Kasahara M, Takada Y, Kozaki K, et al. Functional portal flow competition after auxiliary partial orthotopic living donor liver transplantation in noncirrhotic metabolic liver disease[J]. J Pediatr Surg,2004,39(7):1138-1141.
[18]. Broering DC, Walter J and Bassas AF Overcoming the portal steal phenomenon in auxiliary partial orthotopic liver transplantation by modulation of the venous outflow of the native liver[J]. Liver Transpl,2005,11(9):1140-1143.
[19]. Qian SG, Fung JJ, Demetris AV, et al. Orthotopic liver transplantation in the mouse[J].Transplantation,1991,52(3):562-564.
[1]. Pena MM, Lee J and Thiele DJ A delicate balance:homeostatic control of copper uptake and distribution[J]. J Nutr,1999,129(7):1251-1260.
[2]. Mercer JF and Llanos RM Molecular and cellular aspects of copper transport in developing mammals[J]. J Nutr,2003,133(5 Suppl 1):1481S-1484S.
[3]. Harris ZL and Gitlin JD Genetic and molecular basis for copper toxicity[J]. Am J Clin Nutr,1996,63(5):836S-841S.
[4]. Waggoner DJ, Bartnikas TB and Gitlin JD The role of copper in neurodegenerative disease[J]. Neurobiol Dis,1999,6(4):221-230.
[5]. Loudianos G and Gitlin JD Wilson's disease[J]. Semin Liver Dis, 2000,20(3):353-364.
[6]. Riordan SM and Williams R The Wilson's disease gene and phenotypic diversity[J]. J Hepatol,2001,34(1):165-171.
[7]. Ferenci P, Caca K, Loudianos G, et al. Diagnosis and phenotypic classification of Wilson disease[J]. Liver Int,2003,23(3):139-142.
[8]. Lutsenko S Atp7b-/-mice as a model for studies of Wilson's disease[J]. Biochem Soc Trans,2008,36(Pt 6):1233-1238.
[9]. Schilsky ML, Quintana N, Volenberg I, et al. Spontaneous cholangiofibrosis in Long-Evans Cinnamon rats:a rodent model for Wilson's disease[J]. Lab Anim Sci, 1998,48(2):156-161.
[10]. Huster D, Hoppert M, Lutsenko S, et al. Defective cellular localization of mutant ATP7B in Wilson's disease patients and hepatoma cell lines[J]. Gastroenterology,2003,124(2):335-345.
[11]. Morgan CT, Tsivkovskii R, Kosinsky YA, et al. The distinct functional properties of the nucleotide-binding domain of ATP7B, the human copper-transporting ATPase:analysis of the Wilson disease mutations E1064A, H1069Q, R1151H, and C1104F[J]. J Biol Chem,2004,279(35):36363-36371.
[12]. Packer NH, Pawlak A, Kett WC, et al. Proteome analysis of glycoforms:a review of strategies for the microcharacterisation of glycoproteins separated by two-dimensional polyacrylamide gel electrophoresis[J]. Electrophoresis, 1997,18(3-4):452-460.
[13]. Huster D, Finegold MJ, Morgan CT, et al. Consequences of copper accumulation in the livers of the Atp7b-/-(Wilson disease gene) knockout mice[J]. Am J Pathol,2006,168(2):423-434.
[14]. Biempica L, Rauch H, Quintana N, et al. Morphologic and chemical studies on a murine mutation (toxic milk mice) resulting in hepatic copper toxicosis[J]. Lab Invest,1988,59(4):500-508.
[15]. Haywood S, Loughran M and Batt RM Copper toxicosis and tolerance in the rat. III. Intracellular localization of copper in the liver and kidney [J]. Exp Mol Pathol, 1985,43(2):209-219.
[1]、Ala A, Walker AP, Ashkan K, et al. Wilson's disease[J]. Lancet, 2007,369(9559):397-408.
[2]、Tanzi RE, Petrukhin K, Chernov I, et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene[J]. Nat Genet, 1993,5(4):344-350.
[3]、Bull PC, Thomas GR, Rommens JM, et al. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene[J]. Nat Genet, 1993,5(4):327-337.
[4]、Yamaguchi Y, Heiny ME, Gitlin JD. Isolation and characterization of a human liver cDNA as a candidate gene for Wilson disease, Biochem Biophys Res Commun,1993,197(1):271-277.
[5]、Roelofsen H, Wolters H, Van Luyn MJ, et al. Copper-induced apical trafficking of ATP7B in polarized hepatoma cells provides a mechanism for biliary copper excretion[J].Gastroenterology,2000,119(3):782-93.
[6]> Schaefer M, Roelofsen H, Wolters H, et al. Localization of the Wilson's disease protein in human liver[J]. Gastroenterology,1999,117(6):1380-1385.
[7]、Walshe JM. Wilson's disease; new oral therapy[J].Lancet,1956,270 (6906): 25-26.
[8]、Walshe JM. Management of penicillamine nephropathy in Wilson's disease:a new chelating agent[J]. Lancet,1969,2(7635):1401-1402.
[9]、Brewer GJ, Hedera P, Kluin KJ, et al. Treatment of Wilson disease with ammonium tetrathiomolybdate:III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy [J]. Arch Neurol, 2003,60(3):379-385.
[10]、Brewer GJ, Dick RD, Johnson VD, et al. Treatment of Wilson's disease with zinc:XV long-term follow-up studies[J]. J Lab Clin Med,1998,132(4):264-278.
[11]、Tatsumi Y, Hattori A, Hayashi H, et al. Current state of Wilson disease patients in central Japan[J]. Intern Med,2010,49(9):809-815.
[12]、Moini M, Mistry P, Schilsky ML. Liver transplantation for inherited metabolic disorders of the liver[J]. Curr Opin Organ Transplant,2010,15(3):269-276.
[13]、Duarte-Rojo A, Zepeda-Gomez S, Garcia-Leiva J, et al. Liver transplantation for neurologic Wilson's disease:reflections on two cases within a mexican cohort[J]. Rev Gastroenterol Mex,2009,74(3):218-223.
[14]、Ikegami T, Shiotani S, Ninomiya M, et al. Auxiliary partial orthotopic liver transplantation from living donors[J]. Surgery,2002,131(1 Suppl):S205-210.
[15]、Park YK, Kim BW, Wang HJ, et al. Auxiliary partial orthotopic living donor liver transplantation in a patient with Wilson's disease:a case report[J]. Transplant Proc,2008,40(10):3808-3809.
[16]、Buiakova OI, Xu J, Lutsenko S, et al. Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation [J]. Hum Mol Genet,1999,8(9):1665-1671.
[17]、Huster D, Finegold MJ, Morgan CT, et al. Consequences of copper accumulation in the livers of the Atp7b-/- (Wilson disease gene) knockout mice[J]. Am J Pathol,2006,168(2):423-434.
[18]、Schosinsky KH, Lehmann HP, Beeler ME Measurement of ceruloplasmin from its oxidase activity in serum by use of o-dianisidine dihydrochloride[J]. Clin Chem,1974,20(12):1556-1563.
[19]、Uzman LL. Histochemical localization of copper with rubeanic acid[J]. Lab Invest,1956,5(3):299-305.
[20]、吴志英,赵振华.客观评价肝移植在Wilson病治疗中的地位[J].中华神经科杂志,2007,40(11)：721-722.
[21]、吴志英,王柠,慕容慎行,等.肝豆状核变性基因12号外显子突变特征的研究[J].中华医学杂志,1999,79(6)：422-424.
[22]、吴志英,王柠,林珉婷,等.Wilson病基因突变类型与临床表型的关系[J].中华医学杂志,2003,83(4)：309-311.
[23]、European association for the study of the liver. EASL clinical practice guidelines:Wilson's disease[J]. Journal of hepatology,2012,56:671-685.
[24]、Walshe JM. Copper chelation in patients with Wilson's disease. A comparison of penicillamine and triethylene tetramine dihydrochloride[J]. Q J Med,1973,42:441-452.
[25]、Medici V, Trevisan CP, D'Inca R, et al. Diagnosis and management of Wilson's disease:results of a single center experience [J]. J Clin Gastroenterol,2006,40:936-941.
[26]、Perry AR, Pagliuca A, Fitzsimons EJ, et al. Acquired sideroblastic anaemia induced by a copper-chelating agent[J]. Int J Hematol,1996,64(1):69-72.
[27]、Karunajeewa H, Wall A, Metz J, et al. Cytopenias secondary to copper depletion complicating ammonium tetrathiomolybdate therapy for Wilson's disease[J]. Aust NZ J Med,1998,28:215-216.
[28]、Medici V, Trevisan CP, Bigotto MA, et al. Adverse reation after tetrathiomolybdate treatment for Wilson's disease:a case report[J]. Mov Disord,2006,21:2030-2032.
[29]、Khanna A, Jain A, Eghtesad B, et al. Liver transplantation for Wilson's disese[J]. Surg Clin North Am,1999,79:153-162.
[30]、Schilsky ML, Scheinberg IH, Sternlieb I. Liver transplantation for Wilson's disease:indications and outcome [J]. Hepatology,1994,19:583-587.
[31]、Yoshitoshi EY, Takada Y, Oike F, et al. Long-term outcomes for 32 cases of Wilson's disease after living-donor liver transplantation[J]. Transplantation,2009,87:261-267.
[32]、Schumacher G, Platz KP, Mueller AR, et al. Liver transplantation in neurologic Wilson's disease [J]. Transplant Proc,2001,33:1518-1519.
[33]、Cheng F, Li GQ, Zhang F, et al. Outcomes of living-related liver transplantation for Wilson's disease:a single-center experience in China[J]. Transplantation,2009,87:751-757.
[34]、Wu J, Forbes JR, Chen HS, et al. The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene[J]. Nat Genet, 1994,7(4):541-545.
[35]、Theophilos MB, Cox DW, Mercer JF, et al. The toxic milk mouse is a murine model of Wilson disease[J]. Hum Mol Genet,1996,5(10):1619-1624.
[36]、Lutsenko S. Atp7b-/- mice as a model for studies of Wilson's disease[J]. Biochem Soc Trans,2008,36(Pt 6):1233-1238.
[1]. Ala A, Walker AP, Ashkan K, et al. Wilson's disease[J]. Lancet, 2007,369(9559):397-408.
[2]. Litwin T, Gromadzka G and Czlonkowska A Gender differences in Wilson's disease[J]. J Neurol Sci,2012,312(1-2):31-35.
[3]. Podgaetz E and Chan C Liver transplantation for Wilson s disease:our experience with review of the literature [J]. Ann Hepatol,2003,2(3):131-134.
[4]. Wilson SAK Progressive lenticular degeneration:a familiar nervous disease associated with cirrhosis of the liver[J]. Brain,1912,34(295-507.
[5]. Pfeiffer RF Wilson's Disease[J]. Semin Neurol,2007,27(2):123-132.
[6]. Frydman M, Bonne-Tamir B, Farrer LA, et al. Assignment of the gene for Wilson disease to chromosome 13:linkage to the esterase D locus[J]. Proc Natl Acad Sci U S A,1985,82(6):1819-1821.
[7]. Yamaguchi Y, Heiny ME and Gitlin JD Isolation and characterization of a human liver cDNA as a candidate gene for Wilson disease [J]. Biochem Biophys Res Commun,1993,197(1):271-277.
[8]. Tanzi RE, Petrukhin K, Chernov I, et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene[J]. Nat Genet, 1993,5(4):344-350.
[9]. Bull PC, Thomas GR, Rommens JM, et al. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene[J]. Nat Genet, 1993,5(4):327-337.
[10]. Lee J, Prohaska JR and Thiele DJ Essential role for mammalian copper transporter Ctrl in copper homeostasis and embryonic development[J]. Proc Natl Acad Sci U S A,2001,98(12):6842-6847.
[11]. Kuo YM, Zhou B, Cosco D, et al. The copper transporter CTR1 provides an essential function in mammalian embryonic development [J]. Proc Natl Acad Sci U S A,2001,98(12):6836-6841.
[12]. Walshe JM Wilson's disease. The presenting symptoms[J]. Arch Dis Child, 1962,37(253-256.
[13]. Svetel M, Kozic D, Stefanova E, et al. Dystonia in Wilson's disease[J]. Mov Disord,2001,16(4):719-723.
[14]. Wiebers DO, Hollenhorst RW and Goldstein NP The ophthalmologic manifestations of Wilson's disease[J]. Mayo Clin Proc,1977,52(7):409-416.
[15]. Cairns JE, Williams HP and Walshe JM "Sunflower cataract" in Wilson's disease[J]. Br Med J,1969,3(5662):95-96.
[16]. Schilsky ML, Scheinberg IH and Sternlieb I Liver transplantation for Wilson's disease:indications and outcome[J]. Hepatology,1994,19(3);583-587.
[17]. Factor SM, Cho S, Sternlieb I, et al. The cardiomyopathy of Wilson's disease. Myocardial alterations in nine cases[J]. Virchows Arch A Pathol Anat Histol, 1982,397(3):301-311.
[18]. Okada M, Higashi K, Enomoto S, et al. [A case of Wilson's disease associated with hypoparathyroidism and amenorrhea][J]. Nihon Shokakibyo Gakkai Zasshi,1998,95(5):445-449.
[19]. Kaushansky A, Frydman M, Kaufman H, et al. Endocrine studies of the ovulatory disturbances in Wilson's disease (hepatolenticular degeneration)[J]. Fertil Steril,1987,47(2):270-273.
[20]. Sinha S, Taly AB, Prashanth LK, et al. Successful pregnancies and abortions in symptomatic and asymptomatic Wilson's disease[J]. J Neurol Sci, 2004,217(1):37-40.
[21]. Kalra V, Mahajan S and Kesarwani PK Rare presentation of Wilson's disease: a case report[J]. Int Urol Nephrol,2004,36(2):289-291.
[22]. Gow PJ, Smallwood RA, Angus PW, et al. Diagnosis of Wilson's disease:an experience over three decades[J]. Gut,2000,46(3):415-419.
[23]. Sternlieb I and Scheinberg IH Chronic hepatitis as a first manifestation of Wilson's disease[J]. Ann Intern Med,1972,76(1):59-64.
[24]. Scott J, Gollan JL, Samourian S, et al. Wilson's disease, presenting as chronic active hepatitis[J]. Gastroenterology,1978,74(4):645-651.
[25]. Schilsky ML and Fink S Inherited metabolic liver disease[J]. Curr Opin Gastroenterol,2006,22(3):215-222.
[26]. Strickland GT and Leu ML Wilson's disease. Clinical and laboratory maniestations in 40 patients[J]. Medicine (Baltimore),1975,54(2):113-137.
[27]. Ala A, Borjigin J, Rochwarger A, et al. Wilson disease in septuagenarian siblings:Raising the bar for diagnosis[J]. Hepatology,2005,41(3):668-670.
[28]. Hellman NE and Gitlin JD Ceruloplasmin metabolism and function[J]. Annu Rev Nutr,2002,22(439-458.
[29]. Walshe JM and Yealland M Wilson's disease:the problem of delayed diagnosis[J]. J Neurol Neurosurg Psychiatry,1992,55(8):692-696.
[30]. Barbosa ER, Silveira-Moriyama L, Machado AC, et al. Wilson's disease with myoclonus and white matter lesions[J]. Parkinsonism Relat Disord, 2007,13(3):185-188.
[31]. Bhattacharya K, Velickovic M, Schilsky M, et al. Autonomic cardiovascular reflexes in Wilson's disease[J]. Clin Auton Res,2002,12(3):190-192.
[32]. Meenakshi-Sundaram S, Taly AB, Kamath V, et al. Autonomic dysfunction in Wilson's disease --a clinical and electrophysiological study [J]. Clin Auton Res, 2002,12(3):185-189.
[33]. Dening TR, Berrios GE and Walshe JM Wilson's disease and epilepsy[J]. Brain,1988,111 (Pt 5)(1139-1155.
[34]. Polychronopoulos P, Argyriou AA, Papapetropoulos S, et al. Wilson's disease and benign epilepsy of childhood with centrotemporal (rolandic) spikes[J]. Epilepsy Behav,2006,8(2):438-441.
[35]. Kumar S Wilson's disease presenting as status epilepticus[J]. Indian Pediatr, 2005,42(5):492-493.
[36]. Mueller A, Reuner U, Landis B, et al. Extrapyramidal symptoms in Wilson's disease are associated with olfactory dysfunction[J]. Mov Disord, 2006,21(9):1311-1316.
[37]. Brewer GJ Behavioral abnormalities in Wilson's disease[J]. Adv Neurol, 2005,96(262-274.
[38]. Oder W, Grimm G, Kollegger H, et al. Neurological and neuropsychiatric spectrum of Wilson's disease:a prospective study of 45 cases[J]. J Neurol, 1991,238(5):281-287.
[39]. Dening TR Psychiatric aspects of Wilson's disease[J]. Br J Psychiatry, 1985,147(677-682.
[40]. Kaul A and McMahon D Wilson's disease and offending behaviour--a case report[J]. Med Sci Law,1993,33(4):353-358.
[41]. Akil M, Schwartz JA, Dutchak D, et al. The psychiatric presentations of Wilson's disease [J]. J Neuropsychiatry Clin Neurosci,1991,3(4):377-382.
[42]. Seniow J, Bak T, Gajda J, et al. Cognitive functioning in neurologically symptomatic and asymptomatic forms of Wilson's disease[J]. Mov Disord, 2002,17(5):1077-1083.
[43]. Portala K, Levander S, Westermark K, et al. Pattern of neuropsychological deficits in patients with treated Wilson's disease[J]. Eur Arch Psychiatry Clin Neurosci,2001,251(6):262-268.
[44]. Gronlund J, Nanto-Salonen K, Venetoklis J, et al. Poor cognitive development and abdominal pain:Wilson's disease[J]. Scand J Gastroenterol, 2006,41(3):361-364.
[45]. Innes JR, Strachan IM and Triger DR Unilateral Kayser-Fleischer ring[J]. Br J Ophthalmol,1986,70(6):469-470.
[46]. Sussman W and Scheinberg IH Disappearance of Kayser-Fleischer rings. Effects of penicillamine[J]. Arch Ophthalmol,1969,82(6):738-741.
[47]. Ross ME, Jacobson IM, Dienstag JL, et al. Late-onset Wilson's disease with neurological involvement in the absence of Kayser-Fleischer rings[J]. Ann Neurol, 1985,17(4):411-413.
[48]. Golding DN and Walshe JM Arthropathy of Wilson's disease. Study of clinical and radiological features in 32 patients[J]. Ann Rheum Dis, 1977,36(2):99-111.
[49]. Canelas HM, Carvalho N, Scaff M, et al. Osteoarthropathy of hepatolenticular degeneration[J]. Acta Neurol Scand,1978,57(6):481-487.
[50]. Mindelzun R, Elkin M, Scheinberg IH, et al. Skeletal changes in Wilson's disease. A radiological study[J]. Radiology,1970,94(1):127-132.
[51]. Yarze JC, Martin P, Munoz SJ, et al. Wilson's disease:current status[J]. Am J Med,1992,92(6):643-654.
[52]. McIntyre N, Clink HM, Levi AJ, et al. Hemolytic anemia in Wilson's disease[J]. N Engl J Med,1967,276(8):439-444.
[53]. Sternlieb I Wilson's disease:indications for liver transplants [J]. Hepatology, 1984,4(1 Suppl):15S-17S.
[54]. Donfrid M, Jankovic G, Strahinja R, et al. Idiopathic thrombocytopenia associated with Wilson's disease[J]. Hepatogastroenterology,1998,45(23):1774-1776.
[55]. Wiebers DO, Wilson DM, McLeod RA, et al. Renal stones in Wilson's disease[J]. Am J Med,1979,67(2):249-254.
[56]. Narayanan P, Chetan G and Mahadevan S Wilson's disease presenting as respiratory failure[J]. Indian J Pediatr,2006,73(1):99-100.
[57]. Leu ML, Strickland GT, Wang CC, et al. Skin pigmentation in Wilson's disease[J]. JAMA,1970,211(9):1542-1543.
[58]. Scheinberg IH and Sternlieb I Wilson's Disease[J]. Annu Rev Med, 1965,16(119-134.
[59]. Sinha S, Taly AB, Ravishankar S, et al. Wilson's disease:cranial MRI observations and clinical correlation[J]. Neuroradiology,2006,48(9):613-621.
[60]. El Balkhi S, Trocello JM, Poupon J, et al. Relative exchangeable copper:a new highly sensitive and highly specific biomarker for Wilson's disease diagnosis[J]. Clin Chim Acta,2011,412(23-24):2254-2260.
[61]. Ferenci P, Steindl-Munda P, Vogel W, et al. Diagnostic value of quantitative hepatic copper determination in patients with Wilson's Disease[J]. Clin Gastroenterol Hepatol,2005,3(8):811-818.
[62]. Smallwood RA, Williams HA, Rosenoer VM, et al. Liver-copper levels in liver disease:studies using neutron activation analysis[J]. Lancet, 1968,2(7582):1310-1313.
[63]. Benson GD Hepatic copper accumulation in primary biliary cirrhosis[J]. Yale J Biol Med,1979,52(1):83-88.
[64]. Willeit J and Kiechl SG Wilson's disease with neurological impairment but no Kayser-Fleischer rings[J]. Lancet,1991,337(8754):1426.
[65]. Oracz G, Klimczak-Slaczka D, Sokolowska-Oracz A, et al. [Prevalence of Kayser-Fleischer ring in patients with Wilson's disease] [J]. Klin Oczna, 2005,107(1-3):54-56.
[66]. Gibbs K and Walshe JM A study of the caeruloplasmin concentrations found in 75 patients with Wilson's disease, their kinships and various control groups[J]. Q J Med,1979,48(191):447-463.
[67]. Das SK and Ray K Wilson's disease:an update[J]. Nat Clin Pract Neurol, 2006,2(9):482-493.
[68]. Hoogenraad TU Paradigm shift in treatment of Wilson's disease:zinc therapy now treatment of choice[J]. Brain Dev,2006,28(3):141-146.
[69]. Brewer GJ, Askari F, Lorincz MT, et al. Treatment of Wilson disease with ammonium tetrathiomolybdate:Ⅳ. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease[J]. Arch Neurol,2006,63(4):521-527.
[70]. Walshe JM and Yealland M Chelation treatment of neurological Wilson's disease[J]. Q J Med,1993,86(3):197-204.
[71]. Brewer GJ, Terry CA, Aisen AM, et al. Worsening of neurologic syndrome in patients with Wilson's disease with initial penicillamine therapy[J]. Arch Neurol, 1987,44(5):490-493.
[72]. Hartard C, Weisner B, Dieu C, et al. Wilson's disease with cerebral manifestation:monitoring therapy by CSF copper concentration [J]. J Neurol, 1993,241(2):101-107.
[73]. Prashanth LK, Taly AB, Sinha S, et al. Prognostic factors in patients presenting with severe neurological forms of Wilson's disease[J]. QJM, 2005,98(8):557-563.
[74]. Sternlieb I and Scheinberg IH Penicillamine Therapy for Hepatolenticular Degeneration[J]. JAMA,1964,189(748-754.
[75]. Haggstrom GD, Hirschowitz BI and Flint A Long-term penicillamine therapy for Wilson's disease[J]. South Med J,1980,73(4):530-531.
[76]. Walshe JM Penicillamine:the treatment of first choice for patients with Wilson's disease[J]. Mov Disord,1999,14(4):545-550.
[77]. Cox DW, Prat L, Walshe JM, et al. Twenty-four novel mutations in Wilson disease patients of predominantly European ancestry[J]. Hum Mutat,2005,26(3):280.
[78]. Duarte-Rojo A, Zepeda-Gomez S, Garcia-Leiva J, et al. Liver transplantation for neurologic Wilson's disease:reflections on two cases within a mexican cohort[J]. Rev Gastroenterol Mex,2009,74(3):218-223.
[79]. Korman JD, Volenberg I, Balko J, et al. Screening for Wilson disease in acute liver failure:a comparison of currently available diagnostic tests[J]. Hepatology, 2008,48(4):1167-1174.
[80]. Aagaard NK, Thomsen KL, Holland-Fischer P, et al. A 15-year-old girl with severe hemolytic Wilson's crisis recovered without transplantation after extracorporeal circulation with the Prometheus system[J]. Blood Purif, 2009,28(2):102-107.
[81]. Medici V, Mirante VG, Fassati LR, et al. Liver transplantation for Wilson's disease:The burden of neurological and psychiatric disorders[J]. Liver Transpl, 2005,11(9):1056-1063.
[82]. Yoshitoshi EY, Takada Y, Oike F, et al. Long-term outcomes for 32 cases of Wilson's disease after living-donor liver transplantation[J]. Transplantation, 2009,87(2):261-267.
[83]. Pabon V, Dumortier J, Gincul R, et al. Long-term results of liver transplantation for Wilson's disease[J]. Gastroenterol Clin Biol,2008,32(4):378-381.
[84]. Wang XH, Cheng F, Zhang F, et al. [Living donor liver transplantation treatment of Wilson's disease complicated with neuropathy] [J]. Zhonghua Yi Xue Za Zhi,2003,83(18):1569-1571.
[85]. Sauer V, Siaj R, Todorov T, et al. Overexpressed ATP7B protects mesenchymal stem cells from toxic copper[J]. Biochem Biophys Res Commun, 2010,395(3):307-311. [86]. Malhi H, Joseph B, Schilsky ML, et al. Development of cell therapy
strategies to overcome copper toxicity in the LEC rat model of Wilson disease[J]. Regen Med,2008,3(2):165-173.
[87]. Park SM, Vo K, Lallier M, et al. Hepatocyte transplantation in the Long Evans Cinnamon rat model of Wilson's disease[J]. Cell Transplant,2006,15(1):13-22.
[88]. Allen KJ, Cheah DM, Wright PF, et al. Liver cell transplantation leads to repopulation and functional correction in a mouse model of Wilson's disease [J]. J Gastroenterol Hepatol,2004,19(11):1283-1290.
[89]. Erol I, Alehan F, Ozcay F, et al. Neurologic complications of liver transplantation in pediatric patients with the hepatic form of Wilson's disease[J]. J Child Neurol,2008,23(3):293-300.
[90]. Erol I, Alehan F, Ozcay F, et al. Neurological complications of liver transplantation in pediatric patients:a single center experience [J]. Pediatr Transplant, 2007,11(2):152-159.
[91]. Nazer H, Ede RJ, Mowat AP, et al. Wilson's disease:clinical presentation and use of prognostic index[J]. Gut,1986,27(11):1377-1381.
[92]. Dhawan A, Taylor RM, Cheeseman P, et al. Wilson's disease in children: 37-year experience and revised King's score for liver transplantation [J]. Liver Transpl, 2005,11(4):441-448.
[93]. Petrasek J, Jirsa M, Sperl J, et al. Revised King's College score for liver transplantation in adult patients with Wilson's disease[J]. Liver Transpl, 2007,13(1):55-61.
[94]. Goodrich EO, Jr., Welch HF, Nelson JA, et al. Homotransplantation of the canine liver[J]. Surgery,1956,39(2):244-251.
[95]. Absolon KB, Hagihara PF, Griffen WO, Jr., et al. Experimental and clinical heterotopic liver homotransplantation[J]. Rev Int Hepatol,1965,15(8):1481-1490.
[96]. Le Bihan G, Coquerel A, Houssin D, et al. [Fatal hepatic failure and sodium valproate (author's transl)][J]. Gastroenterol Clin Biol,1982,6(5):477-481.
[97]. Gubernatis G, Pichlmayr R, Kemnitz J, et al. Auxiliary partial orthotopic liver transplantation (APOLT) for fulminant hepatic failure:first successful case report[J]. World J Surg,1991,15(5):660-665; discussion 665-666.
[98]. Kobayashi T, Sato Y, Yamamoto S, et al. Auxiliary partial orthotopic living donor liver transplantation for fulminant hepatic failure with flat electroencephalogram:a case report[J]. Transplant Proc,2010,42(3):990-993.
[99]. Jaeck D, Boudjema K, Audet M, et al. Auxiliary partial orthotopic liver transplantation (APOLT) in the treatment of acute liver failure[J]. J Gastroenterol, 2002,37 Suppl 13(88-91.
[100]. Terpstra OT Auxiliary liver grafting:a new concept in liver transplantation [J]. Lancet,1993,342(8874):758.
[101]. Kasahara M, Takada Y, Egawa H, et al. Auxiliary partial orthotopic living donor liver transplantation:Kyoto University experience [J]. Am J Transplant, 2005,5(3):558-565.
[102]. Park YK, Kim BW, Wang HJ, et al. Auxiliary partial orthotopic living donor liver transplantation in a patient with Wilson's disease:a case report[J]. Transplant Proc,2008,40(10):3808-3809.
[1]. Loudianos G and Gitlin JD Wilson's disease[J]. Semin Liver Dis, 2000,20(3):353-364.
[2]. Harada M Wilson disease and its current problems[J]. Intern Med, 2010,49(9):807-808.
[3]. Alva-Moncayo E, Castro-Tarin M and Gonzalez-Serrano A [Wilson disease. A case report and review of the literature][J]. Rev Med Inst Mex Seguro Soc, 2011,49(3):331-334.
[4]. Hay wood S, Muller T, Muller W, et al. Copper-associated liver disease in North Ronaldsay sheep:a possible animal model for non-Wilsonian hepatic copper toxicosis of infancy and childhood[J]. J Pathol,2001,195(2):264-269.
[5]. Thornburg LP A perspective on copper and liver disease in the dog[J]. J Vet Diagn Invest,2000,12(2):101-110.
[6]. Muller T, Muller W and Feichtinger H Idiopathic copper toxicosis[J]. Am J Clin Nutr,1998,67(5 Suppl):1082S-1086S.
[7]. Elmes ME, Clarkson JP, Mahy NJ, et al. Metallothionein and copper in liver disease with copper retention--a histopathological study[J]. J Pathol, 1989,158(2):131-137.
[8]. Fuentealba C, Guest S, Haywood S, et al. Chronic hepatitis:a retrospective study in 34 dogs[J]. Can Vet J,1997,38(6):365-373.
[9]. Wu J, Forbes JR, Chen HS, et al. The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene[J]. Nat Genet, 1994,7(4):541-545.
[10]. Theophilos MB, Cox DW and Mercer JF The toxic milk mouse is a murine model of Wilson disease[J]. Hum Mol Genet,1996,5(10):1619-1624.
[11]. Lutsenko S Atp7b-/- mice as a model for studies of Wilson's disease[J]. Biochem Soc Trans,2008,36(Pt 6):1233-1238.
[12]. Terada K, Aiba N, Yang XL, et al. Biliary excretion of copper in LEC rat after introduction of copper transporting P-type ATPase, ATP7B[J]. FEBS Lett, 1999,448(1):53-56.
[13]. Cousins RJ Absorption, transport, and hepatic metabolism of copper and zinc: special reference to metallothionein and ceruloplasmin[J]. Physiol Rev, 1985,65(2):238-309.
[14]. Oestreicher P and Cousins RJ Copper and zinc absorption in the rat: mechanism of mutual antagonism[J]. J Nutr,1985,115(2):159-166.
[15]. DiDonato M and Sarkar B Copper transport and its alterations in Menkes and Wilson diseases[J]. Biochim Biophys Acta,1997,1360(1):3-16.
[16]. Linder MC and Hazegh-Azam M Copper biochemistry and molecular biology [J]. Am J Clin Nutr,1996,63(5):797S-811S.
[17]. Harris ED Copper transport:an overview[J]. Proc Soc Exp Biol Med, 1991,196(2):130-140.
[18]. Subramanian I, Vanek ZF and Bronstein JM Diagnosis and treatment of Wilson's disease[J]. Curr Neurol Neurosci Rep,2002,2(4):317-323.
[19]. Kasai N, Osanai T, Miyoshi I, et al. Clinico-pathological studies of LEC rats with hereditary hepatitis and hepatoma in the acute phase of hepatitis[J]. Lab Anim Sci,1990,40(5):502-505.
[20]. Rauch H and Wells AJ The toxic milk mutation, tx, which results in a condition resembling Wilson disease in humans, is linked to mouse chromosome 8[J]. Genomics,1995,29(2):551-552.
[21]. Johnson GF, Gilbertson SR, Goldfischer S, et al. Cytochemical detection of inherited copper toxicosis of Bedlington terriers[J]. Vet Pathol,1984,21(1):57-60.
[22]. Thornburg LP, Shaw D, Dolan M, et al. Hereditary copper toxicosis in West Highland white terrers[J]. Vet Pathol,1986,23(2):148-154.
[23]. Kaplan MM Primary biliary cirrhosis[J]. N Engl J Med, 1996,335(21):1570-1580.
[24]. Miyamura H, Nakanuma Y and Kono N Survey of copper granules in liver biopsy specimens from various liver abnormalities other than Wilson's disease and biliary diseases[J]. Gastroenterol Jpn,1988,23(6):633-638.
[25]. Schilsky ML Wilson disease:genetic basis of copper toxicity and natural history[J]. Semin Liver Dis,1996,16(1):83-95.
[26]. Nanji MS, Nguyen VT, Kawasoe JH, et al. Haplotype and mutation analysis in Japanese patients with Wilson disease[J]. Am J Hum Genet,1997,60(6):1423-1429.
[27]. Scheinberg IH and Sternlieb I Wilson disease and idiopathic copper toxicosis[J]. Am J Clin Nutr,1996,63(5):842S-845S.
[28]. Ferenci P Wilson's disease[J]. Ital J Gastroenterol Hepatol,1999,31(5): 416-425.
[29]. Bull PC, Thomas GR, Rommens JM, et al. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene[J]. Nat Genet, 1993,5(4):327-337.
[30]. Thomas GR, Forbes JR, Roberts EA, et al. The Wilson disease gene: spectrum of mutations and their consequences[J]. Nat Genet,1995,9(2):210-217.
[31]. Pilloni L, Lecca S, Van Eyken P, et al. Value of histochemical stains for copper in the diagnosis of Wilson's disease[J]. Histopathology,1998,33(1):28-33.
[32]. Steindl P, Ferenci P, Dienes HP, et al. Wilson's disease in patients presenting with liver disease:a diagnostic challenge[J]. Gastroenterology,1997,113(1):212-218.
[33]. Bingham MJ, Ong TJ, Summer KH, et al. Physiologic function of the Wilson disease gene product, ATP7B[J]. Am J Clin Nutr,1998,67(5 Suppl):982S-987S.
[34]. Masuda R, Yoshida MC, Sasaki M, et al. Hereditary hepatitis of LEC rats is controlled by a single autosomal recessive gene[J]. Lab Anim,1988,22(2):166-169.
[35]. Cuthbert JA Wilson's disease:a new gene and an animal model for an old disease[J]. J Investig Med,1995,43(4):323-336.
[36]. Kato J, Kobune M, Kohgo Y, et al. Hepatic iron deprivation prevents spontaneous development of fulminant hepatitis and liver cancer in Long-Evans Cinnamon rats[J]. J Clin Invest,1996,98(4):923-929.
[37]. Sternlieb I, Quintana N, Volenberg I, et al. An array of mitochondrial alterations in the hepatocytes of Long-Evans Cinnamon rats[J]. Hepatology, 1995,22(6):1782-1787.
[38]. Downey JS, Bingle CD, Cottrell S, et al. The LEC rat possesses reduced hepatic selenium, contributing to the severity of spontaneous hepatitis and sensitivity to carcinogenesis[J]. Biochem Biophys Res Commun,1998,244(2):463-467.
[39]. Yokoi T, Nagayama S, Kajiwara R, et al. Occurrence of autoimmune antibodies to liver microsomal proteins associated with lethal hepatitis in LEC rats: effects of TJN-101 ((+)-(6S,7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy-6,7-dimethy 1-10,11-methylenedioxy-6-dibenzo[a,c]cyclooctenol) on the development of hepatitis and the autoantibodies[J]. Toxicol Lett,1995,76(1):33-38.
[40]. Yokoi T, Nagayama S, Kajiwara R, et al. Effects of cyclosporin-A and D-penicillamine on the development of hepatitis and the production of antibody to protein disulfide isomerase in LEC rats[J]. Res Commun Mol Pathol Pharmacol, 1994,85(1):73-81.
[41]. Bedard K, Fuentealba IC and Cribb A The Long Evans Cinnamon (LEC) rat develops hepatocellular damage in the absence of antimicrosomal antibodies [J]. Toxicology,2000,146(2-3):101-109.
[42]. Li Y, Togashi Y, Sato S, et al. Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease[J]. J Clin Invest,1991,87(5):1858-1861.
[43]. Rui M and Suzuki KT Copper in plasma reflects its status and subsequent toxicity in the liver of LEC rats[J]. Res Commun Mol Pathol Pharmacol, 1997,98(3):335-346.
[44]. Mori M, Hattori A, Sawaki M, et al. The LEC rat:a model for human hepatitis, liver cancer, and much more[J]. Am J Pathol,1994,144(1):200-204.
[45]. Cheng WS, Govindarajan S and Redeker AG Hepatocellular carcinoma in a case of Wilson's disease[J]. Liver,1992,12(1):42-45.
[46]. Rauch H Toxic milk, a new mutation affecting cooper metabolism in the mouse[J]. J Hered,1983,74(3):141-144.
[47]. Biempica L, Rauch H, Quintana N, et al. Morphologic and chemical studies on a murine mutation (toxic milk mice) resulting in hepatic copper toxicosis [J]. Lab Invest,1988,59(4):500-508.
[48]. Buiakova OI, Xu J, Lutsenko S, et al. Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation[J]. Hum Mol Genet,1999,8(9):1665-1671.
[49]. Michalczyk AA, Rieger J, Allen KJ, et al. Defective localization of the Wilson disease protein (ATP7B) in the mammary gland of the toxic milk mouse and the effects of copper supplementation[J]. Biochem J,2000,352 Pt 2(565-571.
[50]. Llanos RM and Mercer JF The molecular basis of copper homeostasis copper-related disorders[J]. DNA Cell Biol,2002,21(4):259-270.
[51]. Terwel D, Loschmann YN, Schmidt HH, et al. Neuroinflammatory and behavioural changes in the Atp7B mutant mouse model of Wilson's disease[J]. J Neurochem,2011,118(1):105-112.
[52]. Terada K and Sugiyama T The Long-Evans Cinnamon rat:an animal model for Wilson's disease[J]. Pediatr Int,1999,41(4):414-418.
[53]. Coronado V, Nanji M and Cox DW The Jackson toxic milk mouse as a model for copper loading[J]. Mamm Genome,2001,12(10):793-795.
[54]. Huster D, Finegold MJ, Morgan CT, et al. Consequences of copper accumulation in the livers of the Atp7b-/- (Wilson disease gene) knockout mice[J]. Am J Pathol,2006,168(2):423-434.
[55]. Wirth PL and Linder MC Distribution of copper among components of human serum[J]. J Natl Cancer Inst,1985,75(2):277-284.
[56]. van De Sluis B, Rothuizen J, Pearson PL, et al. Identification of a new copper metabolism gene by positional cloning in a purebred dog population[J]. Hum Mol Genet,2002,11(2):165-173.
[57]. van de Sluis BJ, Breen M, Nanji M, et al. Genetic mapping of the copper toxicosis locus in Bedlington terriers to dog chromosome 10, in a region syntenic to human chromosome region 2p13-p16[J]. Hum Mol Genet,1999,8(3):501-507.
[58]. Johnson GF, Zawie DA, Gilbertson SR, et al. Chronic active hepatitis in Doberman pinschers[J]. J Am Vet Med Assoc,1982,180(12):1438-1442.
[59]. Crawford MA, Schall WD, Jensen RK, et al. Chronic active hepatitis in 26 Doberman pinschers[J]. J Am Vet Med Assoc,1985,187(12):1343-1350.
[60]. Speeti M, Eriksson J, Saari S, et al. Lesions of subclinical doberman hepatitis[J]. Vet Pathol,1998,35(5):361-369.
[61]. Hay wood S, Rutgers HC and Christian MK Hepatitis and copper accumulation in Skye terriers[J]. Vet Pathol,1988,25(6):408-414.
[62]. Kaplan MM Primary biliary cirrhosis[J]. Adv Intern Med,1987,32(359-377.
[2]、Qian SG,Fung JJ.Demetris AV,et al.Orthotopic liver transplantation in the mouse[J]. Transplantation,1991,52:562-564.
[3]、He SQ, Atkinson C, Qiao F et al. Ketamine-Xylazine-Acepromazine compared with isoflurane for anesthesia during liver transplantation in rodents [J]. J Am Assoc Lab Anim Sci,2010,49(1):45-51.
[4]、Huang DR,Wu ZJ,Zhu Y.Modified arterialization of orthotopic liver transplantation in a mouse model[J]. Hepatobiliary Pancreat Dis Int,2010,9:264-268.
[5]、Qian S,Fung JJ,Demetris AJ,et al.Allogeneic orthotopic liver transplantation in mice:a preliminary study of rejection across well-defined MHC barriers[J]. Transplant Proc,1991,23:705-706.
[6]、Morita M, Fujino M, Jiang G, et al. PD-1/B7-H1 interaction contribute to the spontaneous acceptance of mouse liver allograft[J]. Am J Transplant,2010,10:40-46.
[1]. Terpstra OT, Schalm SW, Weimar W, et al. Auxiliary partial liver transplantation for end-stage chronic liver disease[J]. N Engl J Med,1988,319(23):1507-1511.
[2]. Gubernatis G, Pichlmayr R, Kemnitz J, et al. Auxiliary partial orthotopic liver transplantation (APOLT) for fulminant hepatic failure:first successful case report[J]. World J Surg,1991,15(5):660-665;discussion 665-666.
[3]. Chen XP An experimental study of auxiliary partial liver allotransplantation in dogs[J]. J Tongji Med Univ,1987,7(1):15-20.
[4]. Park YK, Kim BW, Wang HJ, et al. Auxiliary partial orthotopic living donor liver transplantation in a patient with Wilson's disease:a case report[J]. Transplant Proc, 2008,40(10):3808-3809.
[5]. Faraj W, Dar F, Bartlett A, et al. Auxiliary liver transplantation for acute liver failure in children[J].Ann Surg,2010,251(2):351-356.
[6]. Kobayashi T, Sato Y, Yamamoto S, et al. Auxiliary partial orthotopic living donor liver transplantation for fulminant hepatic failure with flat electroencephalogram:a case report[J].Transplant Proc,2010,42(3):990-993.
[7]. Ko S, Tanaka I, Kanokogi H, et al. Efficacy of auxiliary partial orthotopic liver transplantation for cure of hemophilia in a canine hemophilia A model[J]. Transplant Proc,2005,37(2):1131-1133.
[8]. Fukueda M, Ishizaki N, Hamada N, et al. Porcine model of auxiliary partial orthotopic liver transplantation for acute liver failure[J]. Transplantation, 2006,82(10):1312-1318.
[9]. Peng CH, Shi LB, Zhang HW, et al. Establishment of a new pig model for auxiliary partial orthotopic liver transplantation[J]. World J Gastroenterol, 2005,11 (6):917-921.
[10]. Palmes D, Diet1 KH, Drews G, et al. Auxiliary partial orthotopic liver transplantation:treatment of acute liver failure in a new rat model[J]. Langenbecks Arch Surg,2002,386(7):534-541.
[11]. Ikegami T, Nishizaki T, Yanaga K, et al. A novel auxiliary partial orthotopic liver transplantation model in rats[J]. Eur Surg Res,2000,32(5):267-273.
[12]. Kamada N and Calne RY Orthotopic liver transplantation in the rat. Technique using cuff for portal vein anastomosis and biliary drainage[J]. Transplantation, 1979,28(1):47-50.
[13]. Kobayashi T, Sato Y, Yamamoto S, et al. Feasibility of auxiliary partial living donor liver transplantation for fulminant hepatic failure as an aid for small-for-size graft:single center experience [J]. Transplant Proc,2009,41(1):262-264.
[14]. Matsuura T, Soejima Y and Taguchi T Auxiliary partial orthotopic living donor liver transplantation with a small-for-size graft for congenital absence of the portal vein[J]. Liver Transpl,2010,16(12):1437-1439.
[15]. Bismuth H, Azoulay D, Samuel D, et al. Auxiliary partial orthotopic liver transplantation for fulminant hepatitis. The Paul Brousse experience [J]. Ann Surg, 1996,224(6):712-724; discussion 724-716.
[16]. Hasegawa K, Sugawara Y and Makuuchi M Which is better to overcome the portal steal phenomenon in auxiliary partial orthotopic liver transplantation:inflow or outflow occlusion?[J]. Liver Transpl,2006,12(4):692-693.
[17]. Kasahara M, Takada Y, Kozaki K, et al. Functional portal flow competition after auxiliary partial orthotopic living donor liver transplantation in noncirrhotic metabolic liver disease[J]. J Pediatr Surg,2004,39(7):1138-1141.
[18]. Broering DC, Walter J and Bassas AF Overcoming the portal steal phenomenon in auxiliary partial orthotopic liver transplantation by modulation of the venous outflow of the native liver[J]. Liver Transpl,2005,11(9):1140-1143.
[19]. Qian SG, Fung JJ, Demetris AV, et al. Orthotopic liver transplantation in the mouse[J].Transplantation,1991,52(3):562-564.
[1]. Pena MM, Lee J and Thiele DJ A delicate balance:homeostatic control of copper uptake and distribution[J]. J Nutr,1999,129(7):1251-1260.
[2]. Mercer JF and Llanos RM Molecular and cellular aspects of copper transport in developing mammals[J]. J Nutr,2003,133(5 Suppl 1):1481S-1484S.
[3]. Harris ZL and Gitlin JD Genetic and molecular basis for copper toxicity[J]. Am J Clin Nutr,1996,63(5):836S-841S.
[4]. Waggoner DJ, Bartnikas TB and Gitlin JD The role of copper in neurodegenerative disease[J]. Neurobiol Dis,1999,6(4):221-230.
[5]. Loudianos G and Gitlin JD Wilson's disease[J]. Semin Liver Dis, 2000,20(3):353-364.
[6]. Riordan SM and Williams R The Wilson's disease gene and phenotypic diversity[J]. J Hepatol,2001,34(1):165-171.
[7]. Ferenci P, Caca K, Loudianos G, et al. Diagnosis and phenotypic classification of Wilson disease[J]. Liver Int,2003,23(3):139-142.
[8]. Lutsenko S Atp7b-/-mice as a model for studies of Wilson's disease[J]. Biochem Soc Trans,2008,36(Pt 6):1233-1238.
[9]. Schilsky ML, Quintana N, Volenberg I, et al. Spontaneous cholangiofibrosis in Long-Evans Cinnamon rats:a rodent model for Wilson's disease[J]. Lab Anim Sci, 1998,48(2):156-161.
[10]. Huster D, Hoppert M, Lutsenko S, et al. Defective cellular localization of mutant ATP7B in Wilson's disease patients and hepatoma cell lines[J]. Gastroenterology,2003,124(2):335-345.
[11]. Morgan CT, Tsivkovskii R, Kosinsky YA, et al. The distinct functional properties of the nucleotide-binding domain of ATP7B, the human copper-transporting ATPase:analysis of the Wilson disease mutations E1064A, H1069Q, R1151H, and C1104F[J]. J Biol Chem,2004,279(35):36363-36371.
[12]. Packer NH, Pawlak A, Kett WC, et al. Proteome analysis of glycoforms:a review of strategies for the microcharacterisation of glycoproteins separated by two-dimensional polyacrylamide gel electrophoresis[J]. Electrophoresis, 1997,18(3-4):452-460.
[13]. Huster D, Finegold MJ, Morgan CT, et al. Consequences of copper accumulation in the livers of the Atp7b-/-(Wilson disease gene) knockout mice[J]. Am J Pathol,2006,168(2):423-434.
[14]. Biempica L, Rauch H, Quintana N, et al. Morphologic and chemical studies on a murine mutation (toxic milk mice) resulting in hepatic copper toxicosis[J]. Lab Invest,1988,59(4):500-508.
[15]. Haywood S, Loughran M and Batt RM Copper toxicosis and tolerance in the rat. III. Intracellular localization of copper in the liver and kidney [J]. Exp Mol Pathol, 1985,43(2):209-219.
[1]、Ala A, Walker AP, Ashkan K, et al. Wilson's disease[J]. Lancet, 2007,369(9559):397-408.
[2]、Tanzi RE, Petrukhin K, Chernov I, et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene[J]. Nat Genet, 1993,5(4):344-350.
[3]、Bull PC, Thomas GR, Rommens JM, et al. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene[J]. Nat Genet, 1993,5(4):327-337.
[4]、Yamaguchi Y, Heiny ME, Gitlin JD. Isolation and characterization of a human liver cDNA as a candidate gene for Wilson disease, Biochem Biophys Res Commun,1993,197(1):271-277.
[5]、Roelofsen H, Wolters H, Van Luyn MJ, et al. Copper-induced apical trafficking of ATP7B in polarized hepatoma cells provides a mechanism for biliary copper excretion[J].Gastroenterology,2000,119(3):782-93.
[6]> Schaefer M, Roelofsen H, Wolters H, et al. Localization of the Wilson's disease protein in human liver[J]. Gastroenterology,1999,117(6):1380-1385.
[7]、Walshe JM. Wilson's disease; new oral therapy[J].Lancet,1956,270 (6906): 25-26.
[8]、Walshe JM. Management of penicillamine nephropathy in Wilson's disease:a new chelating agent[J]. Lancet,1969,2(7635):1401-1402.
[9]、Brewer GJ, Hedera P, Kluin KJ, et al. Treatment of Wilson disease with ammonium tetrathiomolybdate:III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy [J]. Arch Neurol, 2003,60(3):379-385.
[10]、Brewer GJ, Dick RD, Johnson VD, et al. Treatment of Wilson's disease with zinc:XV long-term follow-up studies[J]. J Lab Clin Med,1998,132(4):264-278.
[11]、Tatsumi Y, Hattori A, Hayashi H, et al. Current state of Wilson disease patients in central Japan[J]. Intern Med,2010,49(9):809-815.
[12]、Moini M, Mistry P, Schilsky ML. Liver transplantation for inherited metabolic disorders of the liver[J]. Curr Opin Organ Transplant,2010,15(3):269-276.
[13]、Duarte-Rojo A, Zepeda-Gomez S, Garcia-Leiva J, et al. Liver transplantation for neurologic Wilson's disease:reflections on two cases within a mexican cohort[J]. Rev Gastroenterol Mex,2009,74(3):218-223.
[14]、Ikegami T, Shiotani S, Ninomiya M, et al. Auxiliary partial orthotopic liver transplantation from living donors[J]. Surgery,2002,131(1 Suppl):S205-210.
[15]、Park YK, Kim BW, Wang HJ, et al. Auxiliary partial orthotopic living donor liver transplantation in a patient with Wilson's disease:a case report[J]. Transplant Proc,2008,40(10):3808-3809.
[16]、Buiakova OI, Xu J, Lutsenko S, et al. Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation [J]. Hum Mol Genet,1999,8(9):1665-1671.
[17]、Huster D, Finegold MJ, Morgan CT, et al. Consequences of copper accumulation in the livers of the Atp7b-/- (Wilson disease gene) knockout mice[J]. Am J Pathol,2006,168(2):423-434.
[18]、Schosinsky KH, Lehmann HP, Beeler ME Measurement of ceruloplasmin from its oxidase activity in serum by use of o-dianisidine dihydrochloride[J]. Clin Chem,1974,20(12):1556-1563.
[19]、Uzman LL. Histochemical localization of copper with rubeanic acid[J]. Lab Invest,1956,5(3):299-305.
[20]、吴志英,赵振华.客观评价肝移植在Wilson病治疗中的地位[J].中华神经科杂志,2007,40(11)：721-722.
[21]、吴志英,王柠,慕容慎行,等.肝豆状核变性基因12号外显子突变特征的研究[J].中华医学杂志,1999,79(6)：422-424.
[22]、吴志英,王柠,林珉婷,等.Wilson病基因突变类型与临床表型的关系[J].中华医学杂志,2003,83(4)：309-311.
[23]、European association for the study of the liver. EASL clinical practice guidelines:Wilson's disease[J]. Journal of hepatology,2012,56:671-685.
[24]、Walshe JM. Copper chelation in patients with Wilson's disease. A comparison of penicillamine and triethylene tetramine dihydrochloride[J]. Q J Med,1973,42:441-452.
[25]、Medici V, Trevisan CP, D'Inca R, et al. Diagnosis and management of Wilson's disease:results of a single center experience [J]. J Clin Gastroenterol,2006,40:936-941.
[26]、Perry AR, Pagliuca A, Fitzsimons EJ, et al. Acquired sideroblastic anaemia induced by a copper-chelating agent[J]. Int J Hematol,1996,64(1):69-72.
[27]、Karunajeewa H, Wall A, Metz J, et al. Cytopenias secondary to copper depletion complicating ammonium tetrathiomolybdate therapy for Wilson's disease[J]. Aust NZ J Med,1998,28:215-216.
[28]、Medici V, Trevisan CP, Bigotto MA, et al. Adverse reation after tetrathiomolybdate treatment for Wilson's disease:a case report[J]. Mov Disord,2006,21:2030-2032.
[29]、Khanna A, Jain A, Eghtesad B, et al. Liver transplantation for Wilson's disese[J]. Surg Clin North Am,1999,79:153-162.
[30]、Schilsky ML, Scheinberg IH, Sternlieb I. Liver transplantation for Wilson's disease:indications and outcome [J]. Hepatology,1994,19:583-587.
[31]、Yoshitoshi EY, Takada Y, Oike F, et al. Long-term outcomes for 32 cases of Wilson's disease after living-donor liver transplantation[J]. Transplantation,2009,87:261-267.
[32]、Schumacher G, Platz KP, Mueller AR, et al. Liver transplantation in neurologic Wilson's disease [J]. Transplant Proc,2001,33:1518-1519.
[33]、Cheng F, Li GQ, Zhang F, et al. Outcomes of living-related liver transplantation for Wilson's disease:a single-center experience in China[J]. Transplantation,2009,87:751-757.
[34]、Wu J, Forbes JR, Chen HS, et al. The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene[J]. Nat Genet, 1994,7(4):541-545.
[35]、Theophilos MB, Cox DW, Mercer JF, et al. The toxic milk mouse is a murine model of Wilson disease[J]. Hum Mol Genet,1996,5(10):1619-1624.
[36]、Lutsenko S. Atp7b-/- mice as a model for studies of Wilson's disease[J]. Biochem Soc Trans,2008,36(Pt 6):1233-1238.
[1]. Ala A, Walker AP, Ashkan K, et al. Wilson's disease[J]. Lancet, 2007,369(9559):397-408.
[2]. Litwin T, Gromadzka G and Czlonkowska A Gender differences in Wilson's disease[J]. J Neurol Sci,2012,312(1-2):31-35.
[3]. Podgaetz E and Chan C Liver transplantation for Wilson s disease:our experience with review of the literature [J]. Ann Hepatol,2003,2(3):131-134.
[4]. Wilson SAK Progressive lenticular degeneration:a familiar nervous disease associated with cirrhosis of the liver[J]. Brain,1912,34(295-507.
[5]. Pfeiffer RF Wilson's Disease[J]. Semin Neurol,2007,27(2):123-132.
[6]. Frydman M, Bonne-Tamir B, Farrer LA, et al. Assignment of the gene for Wilson disease to chromosome 13:linkage to the esterase D locus[J]. Proc Natl Acad Sci U S A,1985,82(6):1819-1821.
[7]. Yamaguchi Y, Heiny ME and Gitlin JD Isolation and characterization of a human liver cDNA as a candidate gene for Wilson disease [J]. Biochem Biophys Res Commun,1993,197(1):271-277.
[8]. Tanzi RE, Petrukhin K, Chernov I, et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene[J]. Nat Genet, 1993,5(4):344-350.
[9]. Bull PC, Thomas GR, Rommens JM, et al. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene[J]. Nat Genet, 1993,5(4):327-337.
[10]. Lee J, Prohaska JR and Thiele DJ Essential role for mammalian copper transporter Ctrl in copper homeostasis and embryonic development[J]. Proc Natl Acad Sci U S A,2001,98(12):6842-6847.
[11]. Kuo YM, Zhou B, Cosco D, et al. The copper transporter CTR1 provides an essential function in mammalian embryonic development [J]. Proc Natl Acad Sci U S A,2001,98(12):6836-6841.
[12]. Walshe JM Wilson's disease. The presenting symptoms[J]. Arch Dis Child, 1962,37(253-256.
[13]. Svetel M, Kozic D, Stefanova E, et al. Dystonia in Wilson's disease[J]. Mov Disord,2001,16(4):719-723.
[14]. Wiebers DO, Hollenhorst RW and Goldstein NP The ophthalmologic manifestations of Wilson's disease[J]. Mayo Clin Proc,1977,52(7):409-416.
[15]. Cairns JE, Williams HP and Walshe JM "Sunflower cataract" in Wilson's disease[J]. Br Med J,1969,3(5662):95-96.
[16]. Schilsky ML, Scheinberg IH and Sternlieb I Liver transplantation for Wilson's disease:indications and outcome[J]. Hepatology,1994,19(3);583-587.
[17]. Factor SM, Cho S, Sternlieb I, et al. The cardiomyopathy of Wilson's disease. Myocardial alterations in nine cases[J]. Virchows Arch A Pathol Anat Histol, 1982,397(3):301-311.
[18]. Okada M, Higashi K, Enomoto S, et al. [A case of Wilson's disease associated with hypoparathyroidism and amenorrhea][J]. Nihon Shokakibyo Gakkai Zasshi,1998,95(5):445-449.
[19]. Kaushansky A, Frydman M, Kaufman H, et al. Endocrine studies of the ovulatory disturbances in Wilson's disease (hepatolenticular degeneration)[J]. Fertil Steril,1987,47(2):270-273.
[20]. Sinha S, Taly AB, Prashanth LK, et al. Successful pregnancies and abortions in symptomatic and asymptomatic Wilson's disease[J]. J Neurol Sci, 2004,217(1):37-40.
[21]. Kalra V, Mahajan S and Kesarwani PK Rare presentation of Wilson's disease: a case report[J]. Int Urol Nephrol,2004,36(2):289-291.
[22]. Gow PJ, Smallwood RA, Angus PW, et al. Diagnosis of Wilson's disease:an experience over three decades[J]. Gut,2000,46(3):415-419.
[23]. Sternlieb I and Scheinberg IH Chronic hepatitis as a first manifestation of Wilson's disease[J]. Ann Intern Med,1972,76(1):59-64.
[24]. Scott J, Gollan JL, Samourian S, et al. Wilson's disease, presenting as chronic active hepatitis[J]. Gastroenterology,1978,74(4):645-651.
[25]. Schilsky ML and Fink S Inherited metabolic liver disease[J]. Curr Opin Gastroenterol,2006,22(3):215-222.
[26]. Strickland GT and Leu ML Wilson's disease. Clinical and laboratory maniestations in 40 patients[J]. Medicine (Baltimore),1975,54(2):113-137.
[27]. Ala A, Borjigin J, Rochwarger A, et al. Wilson disease in septuagenarian siblings:Raising the bar for diagnosis[J]. Hepatology,2005,41(3):668-670.
[28]. Hellman NE and Gitlin JD Ceruloplasmin metabolism and function[J]. Annu Rev Nutr,2002,22(439-458.
[29]. Walshe JM and Yealland M Wilson's disease:the problem of delayed diagnosis[J]. J Neurol Neurosurg Psychiatry,1992,55(8):692-696.
[30]. Barbosa ER, Silveira-Moriyama L, Machado AC, et al. Wilson's disease with myoclonus and white matter lesions[J]. Parkinsonism Relat Disord, 2007,13(3):185-188.
[31]. Bhattacharya K, Velickovic M, Schilsky M, et al. Autonomic cardiovascular reflexes in Wilson's disease[J]. Clin Auton Res,2002,12(3):190-192.
[32]. Meenakshi-Sundaram S, Taly AB, Kamath V, et al. Autonomic dysfunction in Wilson's disease --a clinical and electrophysiological study [J]. Clin Auton Res, 2002,12(3):185-189.
[33]. Dening TR, Berrios GE and Walshe JM Wilson's disease and epilepsy[J]. Brain,1988,111 (Pt 5)(1139-1155.
[34]. Polychronopoulos P, Argyriou AA, Papapetropoulos S, et al. Wilson's disease and benign epilepsy of childhood with centrotemporal (rolandic) spikes[J]. Epilepsy Behav,2006,8(2):438-441.
[35]. Kumar S Wilson's disease presenting as status epilepticus[J]. Indian Pediatr, 2005,42(5):492-493.
[36]. Mueller A, Reuner U, Landis B, et al. Extrapyramidal symptoms in Wilson's disease are associated with olfactory dysfunction[J]. Mov Disord, 2006,21(9):1311-1316.
[37]. Brewer GJ Behavioral abnormalities in Wilson's disease[J]. Adv Neurol, 2005,96(262-274.
[38]. Oder W, Grimm G, Kollegger H, et al. Neurological and neuropsychiatric spectrum of Wilson's disease:a prospective study of 45 cases[J]. J Neurol, 1991,238(5):281-287.
[39]. Dening TR Psychiatric aspects of Wilson's disease[J]. Br J Psychiatry, 1985,147(677-682.
[40]. Kaul A and McMahon D Wilson's disease and offending behaviour--a case report[J]. Med Sci Law,1993,33(4):353-358.
[41]. Akil M, Schwartz JA, Dutchak D, et al. The psychiatric presentations of Wilson's disease [J]. J Neuropsychiatry Clin Neurosci,1991,3(4):377-382.
[42]. Seniow J, Bak T, Gajda J, et al. Cognitive functioning in neurologically symptomatic and asymptomatic forms of Wilson's disease[J]. Mov Disord, 2002,17(5):1077-1083.
[43]. Portala K, Levander S, Westermark K, et al. Pattern of neuropsychological deficits in patients with treated Wilson's disease[J]. Eur Arch Psychiatry Clin Neurosci,2001,251(6):262-268.
[44]. Gronlund J, Nanto-Salonen K, Venetoklis J, et al. Poor cognitive development and abdominal pain:Wilson's disease[J]. Scand J Gastroenterol, 2006,41(3):361-364.
[45]. Innes JR, Strachan IM and Triger DR Unilateral Kayser-Fleischer ring[J]. Br J Ophthalmol,1986,70(6):469-470.
[46]. Sussman W and Scheinberg IH Disappearance of Kayser-Fleischer rings. Effects of penicillamine[J]. Arch Ophthalmol,1969,82(6):738-741.
[47]. Ross ME, Jacobson IM, Dienstag JL, et al. Late-onset Wilson's disease with neurological involvement in the absence of Kayser-Fleischer rings[J]. Ann Neurol, 1985,17(4):411-413.
[48]. Golding DN and Walshe JM Arthropathy of Wilson's disease. Study of clinical and radiological features in 32 patients[J]. Ann Rheum Dis, 1977,36(2):99-111.
[49]. Canelas HM, Carvalho N, Scaff M, et al. Osteoarthropathy of hepatolenticular degeneration[J]. Acta Neurol Scand,1978,57(6):481-487.
[50]. Mindelzun R, Elkin M, Scheinberg IH, et al. Skeletal changes in Wilson's disease. A radiological study[J]. Radiology,1970,94(1):127-132.
[51]. Yarze JC, Martin P, Munoz SJ, et al. Wilson's disease:current status[J]. Am J Med,1992,92(6):643-654.
[52]. McIntyre N, Clink HM, Levi AJ, et al. Hemolytic anemia in Wilson's disease[J]. N Engl J Med,1967,276(8):439-444.
[53]. Sternlieb I Wilson's disease:indications for liver transplants [J]. Hepatology, 1984,4(1 Suppl):15S-17S.
[54]. Donfrid M, Jankovic G, Strahinja R, et al. Idiopathic thrombocytopenia associated with Wilson's disease[J]. Hepatogastroenterology,1998,45(23):1774-1776.
[55]. Wiebers DO, Wilson DM, McLeod RA, et al. Renal stones in Wilson's disease[J]. Am J Med,1979,67(2):249-254.
[56]. Narayanan P, Chetan G and Mahadevan S Wilson's disease presenting as respiratory failure[J]. Indian J Pediatr,2006,73(1):99-100.
[57]. Leu ML, Strickland GT, Wang CC, et al. Skin pigmentation in Wilson's disease[J]. JAMA,1970,211(9):1542-1543.
[58]. Scheinberg IH and Sternlieb I Wilson's Disease[J]. Annu Rev Med, 1965,16(119-134.
[59]. Sinha S, Taly AB, Ravishankar S, et al. Wilson's disease:cranial MRI observations and clinical correlation[J]. Neuroradiology,2006,48(9):613-621.
[60]. El Balkhi S, Trocello JM, Poupon J, et al. Relative exchangeable copper:a new highly sensitive and highly specific biomarker for Wilson's disease diagnosis[J]. Clin Chim Acta,2011,412(23-24):2254-2260.
[61]. Ferenci P, Steindl-Munda P, Vogel W, et al. Diagnostic value of quantitative hepatic copper determination in patients with Wilson's Disease[J]. Clin Gastroenterol Hepatol,2005,3(8):811-818.
[62]. Smallwood RA, Williams HA, Rosenoer VM, et al. Liver-copper levels in liver disease:studies using neutron activation analysis[J]. Lancet, 1968,2(7582):1310-1313.
[63]. Benson GD Hepatic copper accumulation in primary biliary cirrhosis[J]. Yale J Biol Med,1979,52(1):83-88.
[64]. Willeit J and Kiechl SG Wilson's disease with neurological impairment but no Kayser-Fleischer rings[J]. Lancet,1991,337(8754):1426.
[65]. Oracz G, Klimczak-Slaczka D, Sokolowska-Oracz A, et al. [Prevalence of Kayser-Fleischer ring in patients with Wilson's disease] [J]. Klin Oczna, 2005,107(1-3):54-56.
[66]. Gibbs K and Walshe JM A study of the caeruloplasmin concentrations found in 75 patients with Wilson's disease, their kinships and various control groups[J]. Q J Med,1979,48(191):447-463.
[67]. Das SK and Ray K Wilson's disease:an update[J]. Nat Clin Pract Neurol, 2006,2(9):482-493.
[68]. Hoogenraad TU Paradigm shift in treatment of Wilson's disease:zinc therapy now treatment of choice[J]. Brain Dev,2006,28(3):141-146.
[69]. Brewer GJ, Askari F, Lorincz MT, et al. Treatment of Wilson disease with ammonium tetrathiomolybdate:Ⅳ. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease[J]. Arch Neurol,2006,63(4):521-527.
[70]. Walshe JM and Yealland M Chelation treatment of neurological Wilson's disease[J]. Q J Med,1993,86(3):197-204.
[71]. Brewer GJ, Terry CA, Aisen AM, et al. Worsening of neurologic syndrome in patients with Wilson's disease with initial penicillamine therapy[J]. Arch Neurol, 1987,44(5):490-493.
[72]. Hartard C, Weisner B, Dieu C, et al. Wilson's disease with cerebral manifestation:monitoring therapy by CSF copper concentration [J]. J Neurol, 1993,241(2):101-107.
[73]. Prashanth LK, Taly AB, Sinha S, et al. Prognostic factors in patients presenting with severe neurological forms of Wilson's disease[J]. QJM, 2005,98(8):557-563.
[74]. Sternlieb I and Scheinberg IH Penicillamine Therapy for Hepatolenticular Degeneration[J]. JAMA,1964,189(748-754.
[75]. Haggstrom GD, Hirschowitz BI and Flint A Long-term penicillamine therapy for Wilson's disease[J]. South Med J,1980,73(4):530-531.
[76]. Walshe JM Penicillamine:the treatment of first choice for patients with Wilson's disease[J]. Mov Disord,1999,14(4):545-550.
[77]. Cox DW, Prat L, Walshe JM, et al. Twenty-four novel mutations in Wilson disease patients of predominantly European ancestry[J]. Hum Mutat,2005,26(3):280.
[78]. Duarte-Rojo A, Zepeda-Gomez S, Garcia-Leiva J, et al. Liver transplantation for neurologic Wilson's disease:reflections on two cases within a mexican cohort[J]. Rev Gastroenterol Mex,2009,74(3):218-223.
[79]. Korman JD, Volenberg I, Balko J, et al. Screening for Wilson disease in acute liver failure:a comparison of currently available diagnostic tests[J]. Hepatology, 2008,48(4):1167-1174.
[80]. Aagaard NK, Thomsen KL, Holland-Fischer P, et al. A 15-year-old girl with severe hemolytic Wilson's crisis recovered without transplantation after extracorporeal circulation with the Prometheus system[J]. Blood Purif, 2009,28(2):102-107.
[81]. Medici V, Mirante VG, Fassati LR, et al. Liver transplantation for Wilson's disease:The burden of neurological and psychiatric disorders[J]. Liver Transpl, 2005,11(9):1056-1063.
[82]. Yoshitoshi EY, Takada Y, Oike F, et al. Long-term outcomes for 32 cases of Wilson's disease after living-donor liver transplantation[J]. Transplantation, 2009,87(2):261-267.
[83]. Pabon V, Dumortier J, Gincul R, et al. Long-term results of liver transplantation for Wilson's disease[J]. Gastroenterol Clin Biol,2008,32(4):378-381.
[84]. Wang XH, Cheng F, Zhang F, et al. [Living donor liver transplantation treatment of Wilson's disease complicated with neuropathy] [J]. Zhonghua Yi Xue Za Zhi,2003,83(18):1569-1571.
[85]. Sauer V, Siaj R, Todorov T, et al. Overexpressed ATP7B protects mesenchymal stem cells from toxic copper[J]. Biochem Biophys Res Commun, 2010,395(3):307-311. [86]. Malhi H, Joseph B, Schilsky ML, et al. Development of cell therapy
strategies to overcome copper toxicity in the LEC rat model of Wilson disease[J]. Regen Med,2008,3(2):165-173.
[87]. Park SM, Vo K, Lallier M, et al. Hepatocyte transplantation in the Long Evans Cinnamon rat model of Wilson's disease[J]. Cell Transplant,2006,15(1):13-22.
[88]. Allen KJ, Cheah DM, Wright PF, et al. Liver cell transplantation leads to repopulation and functional correction in a mouse model of Wilson's disease [J]. J Gastroenterol Hepatol,2004,19(11):1283-1290.
[89]. Erol I, Alehan F, Ozcay F, et al. Neurologic complications of liver transplantation in pediatric patients with the hepatic form of Wilson's disease[J]. J Child Neurol,2008,23(3):293-300.
[90]. Erol I, Alehan F, Ozcay F, et al. Neurological complications of liver transplantation in pediatric patients:a single center experience [J]. Pediatr Transplant, 2007,11(2):152-159.
[91]. Nazer H, Ede RJ, Mowat AP, et al. Wilson's disease:clinical presentation and use of prognostic index[J]. Gut,1986,27(11):1377-1381.
[92]. Dhawan A, Taylor RM, Cheeseman P, et al. Wilson's disease in children: 37-year experience and revised King's score for liver transplantation [J]. Liver Transpl, 2005,11(4):441-448.
[93]. Petrasek J, Jirsa M, Sperl J, et al. Revised King's College score for liver transplantation in adult patients with Wilson's disease[J]. Liver Transpl, 2007,13(1):55-61.
[94]. Goodrich EO, Jr., Welch HF, Nelson JA, et al. Homotransplantation of the canine liver[J]. Surgery,1956,39(2):244-251.
[95]. Absolon KB, Hagihara PF, Griffen WO, Jr., et al. Experimental and clinical heterotopic liver homotransplantation[J]. Rev Int Hepatol,1965,15(8):1481-1490.
[96]. Le Bihan G, Coquerel A, Houssin D, et al. [Fatal hepatic failure and sodium valproate (author's transl)][J]. Gastroenterol Clin Biol,1982,6(5):477-481.
[97]. Gubernatis G, Pichlmayr R, Kemnitz J, et al. Auxiliary partial orthotopic liver transplantation (APOLT) for fulminant hepatic failure:first successful case report[J]. World J Surg,1991,15(5):660-665; discussion 665-666.
[98]. Kobayashi T, Sato Y, Yamamoto S, et al. Auxiliary partial orthotopic living donor liver transplantation for fulminant hepatic failure with flat electroencephalogram:a case report[J]. Transplant Proc,2010,42(3):990-993.
[99]. Jaeck D, Boudjema K, Audet M, et al. Auxiliary partial orthotopic liver transplantation (APOLT) in the treatment of acute liver failure[J]. J Gastroenterol, 2002,37 Suppl 13(88-91.
[100]. Terpstra OT Auxiliary liver grafting:a new concept in liver transplantation [J]. Lancet,1993,342(8874):758.
[101]. Kasahara M, Takada Y, Egawa H, et al. Auxiliary partial orthotopic living donor liver transplantation:Kyoto University experience [J]. Am J Transplant, 2005,5(3):558-565.
[102]. Park YK, Kim BW, Wang HJ, et al. Auxiliary partial orthotopic living donor liver transplantation in a patient with Wilson's disease:a case report[J]. Transplant Proc,2008,40(10):3808-3809.
[1]. Loudianos G and Gitlin JD Wilson's disease[J]. Semin Liver Dis, 2000,20(3):353-364.
[2]. Harada M Wilson disease and its current problems[J]. Intern Med, 2010,49(9):807-808.
[3]. Alva-Moncayo E, Castro-Tarin M and Gonzalez-Serrano A [Wilson disease. A case report and review of the literature][J]. Rev Med Inst Mex Seguro Soc, 2011,49(3):331-334.
[4]. Hay wood S, Muller T, Muller W, et al. Copper-associated liver disease in North Ronaldsay sheep:a possible animal model for non-Wilsonian hepatic copper toxicosis of infancy and childhood[J]. J Pathol,2001,195(2):264-269.
[5]. Thornburg LP A perspective on copper and liver disease in the dog[J]. J Vet Diagn Invest,2000,12(2):101-110.
[6]. Muller T, Muller W and Feichtinger H Idiopathic copper toxicosis[J]. Am J Clin Nutr,1998,67(5 Suppl):1082S-1086S.
[7]. Elmes ME, Clarkson JP, Mahy NJ, et al. Metallothionein and copper in liver disease with copper retention--a histopathological study[J]. J Pathol, 1989,158(2):131-137.
[8]. Fuentealba C, Guest S, Haywood S, et al. Chronic hepatitis:a retrospective study in 34 dogs[J]. Can Vet J,1997,38(6):365-373.
[9]. Wu J, Forbes JR, Chen HS, et al. The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene[J]. Nat Genet, 1994,7(4):541-545.
[10]. Theophilos MB, Cox DW and Mercer JF The toxic milk mouse is a murine model of Wilson disease[J]. Hum Mol Genet,1996,5(10):1619-1624.
[11]. Lutsenko S Atp7b-/- mice as a model for studies of Wilson's disease[J]. Biochem Soc Trans,2008,36(Pt 6):1233-1238.
[12]. Terada K, Aiba N, Yang XL, et al. Biliary excretion of copper in LEC rat after introduction of copper transporting P-type ATPase, ATP7B[J]. FEBS Lett, 1999,448(1):53-56.
[13]. Cousins RJ Absorption, transport, and hepatic metabolism of copper and zinc: special reference to metallothionein and ceruloplasmin[J]. Physiol Rev, 1985,65(2):238-309.
[14]. Oestreicher P and Cousins RJ Copper and zinc absorption in the rat: mechanism of mutual antagonism[J]. J Nutr,1985,115(2):159-166.
[15]. DiDonato M and Sarkar B Copper transport and its alterations in Menkes and Wilson diseases[J]. Biochim Biophys Acta,1997,1360(1):3-16.
[16]. Linder MC and Hazegh-Azam M Copper biochemistry and molecular biology [J]. Am J Clin Nutr,1996,63(5):797S-811S.
[17]. Harris ED Copper transport:an overview[J]. Proc Soc Exp Biol Med, 1991,196(2):130-140.
[18]. Subramanian I, Vanek ZF and Bronstein JM Diagnosis and treatment of Wilson's disease[J]. Curr Neurol Neurosci Rep,2002,2(4):317-323.
[19]. Kasai N, Osanai T, Miyoshi I, et al. Clinico-pathological studies of LEC rats with hereditary hepatitis and hepatoma in the acute phase of hepatitis[J]. Lab Anim Sci,1990,40(5):502-505.
[20]. Rauch H and Wells AJ The toxic milk mutation, tx, which results in a condition resembling Wilson disease in humans, is linked to mouse chromosome 8[J]. Genomics,1995,29(2):551-552.
[21]. Johnson GF, Gilbertson SR, Goldfischer S, et al. Cytochemical detection of inherited copper toxicosis of Bedlington terriers[J]. Vet Pathol,1984,21(1):57-60.
[22]. Thornburg LP, Shaw D, Dolan M, et al. Hereditary copper toxicosis in West Highland white terrers[J]. Vet Pathol,1986,23(2):148-154.
[23]. Kaplan MM Primary biliary cirrhosis[J]. N Engl J Med, 1996,335(21):1570-1580.
[24]. Miyamura H, Nakanuma Y and Kono N Survey of copper granules in liver biopsy specimens from various liver abnormalities other than Wilson's disease and biliary diseases[J]. Gastroenterol Jpn,1988,23(6):633-638.
[25]. Schilsky ML Wilson disease:genetic basis of copper toxicity and natural history[J]. Semin Liver Dis,1996,16(1):83-95.
[26]. Nanji MS, Nguyen VT, Kawasoe JH, et al. Haplotype and mutation analysis in Japanese patients with Wilson disease[J]. Am J Hum Genet,1997,60(6):1423-1429.
[27]. Scheinberg IH and Sternlieb I Wilson disease and idiopathic copper toxicosis[J]. Am J Clin Nutr,1996,63(5):842S-845S.
[28]. Ferenci P Wilson's disease[J]. Ital J Gastroenterol Hepatol,1999,31(5): 416-425.
[29]. Bull PC, Thomas GR, Rommens JM, et al. The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene[J]. Nat Genet, 1993,5(4):327-337.
[30]. Thomas GR, Forbes JR, Roberts EA, et al. The Wilson disease gene: spectrum of mutations and their consequences[J]. Nat Genet,1995,9(2):210-217.
[31]. Pilloni L, Lecca S, Van Eyken P, et al. Value of histochemical stains for copper in the diagnosis of Wilson's disease[J]. Histopathology,1998,33(1):28-33.
[32]. Steindl P, Ferenci P, Dienes HP, et al. Wilson's disease in patients presenting with liver disease:a diagnostic challenge[J]. Gastroenterology,1997,113(1):212-218.
[33]. Bingham MJ, Ong TJ, Summer KH, et al. Physiologic function of the Wilson disease gene product, ATP7B[J]. Am J Clin Nutr,1998,67(5 Suppl):982S-987S.
[34]. Masuda R, Yoshida MC, Sasaki M, et al. Hereditary hepatitis of LEC rats is controlled by a single autosomal recessive gene[J]. Lab Anim,1988,22(2):166-169.
[35]. Cuthbert JA Wilson's disease:a new gene and an animal model for an old disease[J]. J Investig Med,1995,43(4):323-336.
[36]. Kato J, Kobune M, Kohgo Y, et al. Hepatic iron deprivation prevents spontaneous development of fulminant hepatitis and liver cancer in Long-Evans Cinnamon rats[J]. J Clin Invest,1996,98(4):923-929.
[37]. Sternlieb I, Quintana N, Volenberg I, et al. An array of mitochondrial alterations in the hepatocytes of Long-Evans Cinnamon rats[J]. Hepatology, 1995,22(6):1782-1787.
[38]. Downey JS, Bingle CD, Cottrell S, et al. The LEC rat possesses reduced hepatic selenium, contributing to the severity of spontaneous hepatitis and sensitivity to carcinogenesis[J]. Biochem Biophys Res Commun,1998,244(2):463-467.
[39]. Yokoi T, Nagayama S, Kajiwara R, et al. Occurrence of autoimmune antibodies to liver microsomal proteins associated with lethal hepatitis in LEC rats: effects of TJN-101 ((+)-(6S,7S,R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy-6,7-dimethy 1-10,11-methylenedioxy-6-dibenzo[a,c]cyclooctenol) on the development of hepatitis and the autoantibodies[J]. Toxicol Lett,1995,76(1):33-38.
[40]. Yokoi T, Nagayama S, Kajiwara R, et al. Effects of cyclosporin-A and D-penicillamine on the development of hepatitis and the production of antibody to protein disulfide isomerase in LEC rats[J]. Res Commun Mol Pathol Pharmacol, 1994,85(1):73-81.
[41]. Bedard K, Fuentealba IC and Cribb A The Long Evans Cinnamon (LEC) rat develops hepatocellular damage in the absence of antimicrosomal antibodies [J]. Toxicology,2000,146(2-3):101-109.
[42]. Li Y, Togashi Y, Sato S, et al. Spontaneous hepatic copper accumulation in Long-Evans Cinnamon rats with hereditary hepatitis. A model of Wilson's disease[J]. J Clin Invest,1991,87(5):1858-1861.
[43]. Rui M and Suzuki KT Copper in plasma reflects its status and subsequent toxicity in the liver of LEC rats[J]. Res Commun Mol Pathol Pharmacol, 1997,98(3):335-346.
[44]. Mori M, Hattori A, Sawaki M, et al. The LEC rat:a model for human hepatitis, liver cancer, and much more[J]. Am J Pathol,1994,144(1):200-204.
[45]. Cheng WS, Govindarajan S and Redeker AG Hepatocellular carcinoma in a case of Wilson's disease[J]. Liver,1992,12(1):42-45.
[46]. Rauch H Toxic milk, a new mutation affecting cooper metabolism in the mouse[J]. J Hered,1983,74(3):141-144.
[47]. Biempica L, Rauch H, Quintana N, et al. Morphologic and chemical studies on a murine mutation (toxic milk mice) resulting in hepatic copper toxicosis [J]. Lab Invest,1988,59(4):500-508.
[48]. Buiakova OI, Xu J, Lutsenko S, et al. Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation[J]. Hum Mol Genet,1999,8(9):1665-1671.
[49]. Michalczyk AA, Rieger J, Allen KJ, et al. Defective localization of the Wilson disease protein (ATP7B) in the mammary gland of the toxic milk mouse and the effects of copper supplementation[J]. Biochem J,2000,352 Pt 2(565-571.
[50]. Llanos RM and Mercer JF The molecular basis of copper homeostasis copper-related disorders[J]. DNA Cell Biol,2002,21(4):259-270.
[51]. Terwel D, Loschmann YN, Schmidt HH, et al. Neuroinflammatory and behavioural changes in the Atp7B mutant mouse model of Wilson's disease[J]. J Neurochem,2011,118(1):105-112.
[52]. Terada K and Sugiyama T The Long-Evans Cinnamon rat:an animal model for Wilson's disease[J]. Pediatr Int,1999,41(4):414-418.
[53]. Coronado V, Nanji M and Cox DW The Jackson toxic milk mouse as a model for copper loading[J]. Mamm Genome,2001,12(10):793-795.
[54]. Huster D, Finegold MJ, Morgan CT, et al. Consequences of copper accumulation in the livers of the Atp7b-/- (Wilson disease gene) knockout mice[J]. Am J Pathol,2006,168(2):423-434.
[55]. Wirth PL and Linder MC Distribution of copper among components of human serum[J]. J Natl Cancer Inst,1985,75(2):277-284.
[56]. van De Sluis B, Rothuizen J, Pearson PL, et al. Identification of a new copper metabolism gene by positional cloning in a purebred dog population[J]. Hum Mol Genet,2002,11(2):165-173.
[57]. van de Sluis BJ, Breen M, Nanji M, et al. Genetic mapping of the copper toxicosis locus in Bedlington terriers to dog chromosome 10, in a region syntenic to human chromosome region 2p13-p16[J]. Hum Mol Genet,1999,8(3):501-507.
[58]. Johnson GF, Zawie DA, Gilbertson SR, et al. Chronic active hepatitis in Doberman pinschers[J]. J Am Vet Med Assoc,1982,180(12):1438-1442.
[59]. Crawford MA, Schall WD, Jensen RK, et al. Chronic active hepatitis in 26 Doberman pinschers[J]. J Am Vet Med Assoc,1985,187(12):1343-1350.
[60]. Speeti M, Eriksson J, Saari S, et al. Lesions of subclinical doberman hepatitis[J]. Vet Pathol,1998,35(5):361-369.
[61]. Hay wood S, Rutgers HC and Christian MK Hepatitis and copper accumulation in Skye terriers[J]. Vet Pathol,1988,25(6):408-414.
[62]. Kaplan MM Primary biliary cirrhosis[J]. Adv Intern Med,1987,32(359-377.