囊性纤维化动物疾病模型的研究进展
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摘要
囊性纤维化(cystic fibrosis,CF)是由编码囊性纤维化跨膜传导调节因子(cystic fibrosis transmembrane conductance regulator,CFTR)的基因突变引起的遗传性疾病。CFTR是一种重要的氯离子通道,突变会引起CF病变,临床表现为气道黏膜纤毛清除率降低、细菌定殖和以中性粒细胞为主的慢性炎症反应。通过建立多种CF动物模型,可以对该病的病理学改变、发病机制和药物治疗等多方面进行分析。现着重对CF的发病机制、临床表现以及对三种动物模型(小鼠、猪和雪貂)的基本病理表型进行综述。
引文
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[25] Johnson-Delaney C A. Ferret nutrition[J]. Vet Clin North Am Exot Anim Pract,2014,17(3):449-470.
[26] Sun X,Olivier A K,Yi Y,et al. Gastrointestinal pathology in juvenile and adult CFTR-knockout ferrets[J]. Am J Pathol,2014,184(5):1309-1322.
[2] Frayman K B,Armstrong D S,Carzino R,et al. The lower airway microbiota in early cystic fibrosis lung disease:a longitudinal analysis[J]. Thorax,2017,72(12):1104-1112.
[3] Rotti P G,Xie W,Poudel A,et al. Pancreatic and islet remodeling in cystic fibrosis transmembrane conductance regulator(CFTR)knockout ferrets[J]. Am J Pathol,2018,188(4):876-890.
[4] Snouwaert J N,Brigman K K,Latour A M,et al. An animal model for cystic fibrosis made by gene targeting[J]. Science,1992,257(5073):1083-1088.
[5] Davidson D J,Dorin J R. The CF mouse:an important tool for studying cystic fibrosis[J]. Expert Rev Mol Med,2001,2001:1-27.
[6] Philp A R,Riquelme T T,MillaR-Büchner P,et al. Kcnn4 is a modifier gene of intestinal cystic fibrosis preventing lethality in the CftR-F508del mouse[J]. Sci Rep,2018,8(1):9320.
[7] Veltman M,Stolarczyk M,Radzioch D,et al. Correction of lung inflammation in a F508del CFTR murine cystic fibrosis model by the sphingosine-1-phosphate lyase inhibitor LX2931[J]. Am J Physiol Lung Cell Mol Physiol,2016,311(5):L1000-L1014.
[8] Kotha K,Clancy J P. Ivacaftor treatment of cystic fibrosis patients with the G551D mutation:a review of the evidence[J]. Ther Adv Respir Dis,2013,7(5):288-296.
[9] Davidson D J,Rolfe M. Mouse models of cystic fibrosis[J].Trends Genet,2001,17(10):S29-S37.
[10] Ostedgaard L S,Meyerholz D K,Chen J H,et al. The Delta F508mutation causes CFTR misprocessing and cystic fibrosis-like disease in pigs[J]. Sci Transl Med,2011,3(74):74ra24.
[11] Adam R J,Michalski A S,Bauer C,et al. Air trapping and airflow obstruction in newborn cystic fibrosis piglets[J]. Am J Respir Crit Care Med,2013,188(12):1434-1441.
[12] Rogers C S,Stoltz D A,Meyerholz D K,et al. Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs[J]. Science,2008,321(5897):1837-1841.
[13]李瑞琴,孙洁,李伟,等.肺纤维化前期肺组织中ICAM-1、TGF-β、CTGF的表达及其镜下形态改变的动态观察[J].临床与实验病理学杂志,2016,32(7):786-791.
[14] Chen J H,Stoltz D A,Karp P H,et al. Loss of anion transport without increased sodium absorption characterizes newborn porcine cystic fibrosis airway epithelia[J]. Cell,2010,143(6):911-923.
[15] Meyerholz D K,Stoltz D A,Pezzulo A A,et al. Pathology of gastrointestinal organs in a porcine model of cystic fibrosis[J]. Am J Pathol,2010,176(3):1377-1389.
[16] van der Doef H P,Kokke F T,van der Ent C K,et al. Intestinal obstruction syndromes in cystic fibrosis:meconium ileus,distal intestinal obstruction syndrome,and constipation[J]. Curr Gastroenterol Rep,2011,13(3):265-270.
[17] O’Sullivan B P,Baker D,Leung K G,et al. Evolution of pancreatic function during the first year in infants with cystic fibrosis[J].J Pediatr,2013,162(4):808-812.
[18] Uc A,Giriyappa R,Meyerholz D K,et al. Pancreatic and biliary secretion are both altered in cystic fibrosis pigs[J]. Am J Physiol Gastrointest Liver Physiol,2012,303:G961-G968.
[19] Krammer F,Hai R,Yondola M,et al. Assessment of influenza virus hemagglutinin stalk-based immunity in ferrets[J]. J Virol,2014,88(6):3432-3442.
[20] Dajani R,Zhang Y,Taft P J,et al. Lysozyme secretion by submucosal glands protects the airway from bacterial infection[J].Am J Respir Cell Mol Biol,2005,32(6):548-552.
[21] Mc Carron A,Donnelley M,Parsons D. Airway disease phenotypes in animal models of cystic fibrosis[J]. Respir Res,2018,19(1):54.
[22] Sun X,Yan Z,Yi Y,et al. Adeno-associated virus-targeted disruption of the CFTR gene in cloned ferrets[J]. J Clin Invest,2008,118(4):1578-1583.
[23] Keiser N W,Birket S E,Evans I A,et al. Defective innate immunity and hyperinflammation in newborn cystic fibrosis transmembrane conductance regulator-knockout ferret lungs[J]. Am J Respir Cell Mol Biol,2015,52(6):683-694.
[24] Sun X,Sui H,Fisher J T,et al. Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis[J]. J Clin Invest,2010,120(9):3149-3160.
[25] Johnson-Delaney C A. Ferret nutrition[J]. Vet Clin North Am Exot Anim Pract,2014,17(3):449-470.
[26] Sun X,Olivier A K,Yi Y,et al. Gastrointestinal pathology in juvenile and adult CFTR-knockout ferrets[J]. Am J Pathol,2014,184(5):1309-1322.