Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor
Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor
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DOI：
10.1038/ng0396-280
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发表时间：
1996-03-01
期刊：
影响因子：
30.8
通讯作者：
Tsui, LC
中科院分区：
文献类型：
--
作者：
Rozmahel, R;Wilschanski, M;Tsui, LC
囊性纤维化跨膜传导调节因子(CFTR)缺乏的小鼠通常死于肠梗阻，我们创造了CFTR缺乏的小鼠，并证明了不同近交系回交和杂交后代的存活时间延长，这表明疾病严重程度的调节是由遗传决定的。基因组扫描显示，主要修饰基因位于小鼠7号染色体着丝粒附近。对存活时间较长的小鼠的电生理学研究表明，氯离子和钠离子转运异常的部分纠正可以通过上调钙激活的氯离子电导来解释。在我们的CFTR(M1HSC)/CFT(Rm1HSC)小鼠中识别修饰基因将为了解CF患者中观察到的异质性疾病表现提供重要的洞察力。
Mice that have been made deficient for the cystic fibrosis transmembrane conductance regulator (Cftr) usually die of intestinal obstruction, We have created Cftr-deficient mice and demonstrate prolonged survival among backcross and intercross progeny with different inbred strains, suggesting that modulation of disease severity is genetically determined. A genome scan showed that the major modifier locus maps near the centromere of mouse chromosome 7. Electrophysiological studies on mice with prolonged survival show that the partial rectification of Cl- and Na+ ion transport abnormalities can be explained in part by up-regulation of a calcium-activated Cl- conductance, Identification of modifier genes in our Cftr(m1HSC)/Cft(rm1HSC) mice should provide important insight into the heterogeneous disease presentation observed among CF patients.