Cystic fibrosis mice carrying the missense mutation G551D replicate human genotype phenotype correlations
Cystic fibrosis mice carrying the missense mutation G551D replicate human genotype phenotype correlations
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DOI：
10.1002/j.1460-2075.1996.tb00432.x
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发表时间：
1996-03-01
期刊：
影响因子：
11.4
通讯作者：
Wainwright, BJ
中科院分区：
文献类型：
--
作者：
Delaney, SJ;Alton, EWFW;Wainwright, BJ
我们已经通过一步基因打靶程序产生了一只囊性纤维化跨膜传导调节基因(CFTR)中携带人G551D突变的小鼠，这些突变小鼠表现出囊性纤维化病理，但致命肠梗阻的风险比‘空’突变小鼠低，与G551D患者胎粪性肠梗阻的发生率一致，G551D突变小鼠显示出与CFTR相关的氯转运大大减少，显示出介于CFTR(M1UNC)替换(‘空’)和CFTR(M1HGU)插入(剩余活性)突变之间的活性，相当于野生型CFTR活性的4%，这些动物的长期存活应该为研究囊性纤维化提供了一个很好的模型，它们说明了携带相关突变的小鼠模型在检查基因-表型相关性方面的价值。
We have generated a mouse carrying the human G551D mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR) by a one-step gene targeting procedure, These mutant mice show cystic fibrosis pathology but have a reduced risk of fatal intestinal blockage compared with 'null' mutants, in keeping with the reduced incidence of meconium ileus in G551D patients, The G551D mutant mice show greatly reduced CFTR-related chloride transport, displaying activity intermediate between that of cftr(m1UNC) replacement ('null') and cftr(m1HGU) insertional (residual activity) mutants and equivalent to similar to 4% of wild-type CFTR activity, The long-term survival of these animals should provide an excellent model with which to study cystic fibrosis, and they illustrate the value of mouse models carrying relevant mutations for examining genotype-phenotype correlations.