DEFECTIVE EPITHELIAL CHLORIDE TRANSPORT IN A GENE-TARGETED MOUSE MODEL OF CYSTIC-FIBROSIS
DEFECTIVE EPITHELIAL CHLORIDE TRANSPORT IN A GENE-TARGETED MOUSE MODEL OF CYSTIC-FIBROSIS
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DOI：
10.1126/science.257.5073.1125
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发表时间：
1992-08-21
期刊：
影响因子：
56.9
通讯作者：
BOUCHER, RC
中科院分区：
文献类型：
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作者：
CLARKE, LL;GRUBB, BR;BOUCHER, RC
囊性纤维化跨膜电导调节器 (CFTR) 基因编码腺苷 3',5'-单磷酸 (环 AMP) 激活的氯离子通道。在囊性纤维化 (CF) 患者中，由于基因突变导致 CFTR 功能丧失，导致环 AMP 介导的上皮细胞氯离子分泌缺陷。由于其作为 CF 动物模型的潜在作用，对小鼠 CFTR 基因 [CFTR(-/-)] 进行靶向破坏的小鼠进行了上皮氯转运异常的测试。在新鲜切除的肠道组织和近端气道培养的上皮细胞中，与同窝对照小鼠相比，CFTR(-/-) 小鼠中不存在环磷酸腺苷激活的氯化物分泌反应。因此，根据人类 CF 上皮细胞的研究预测，鼠 CFTR 基因的破坏会导致氯离子转运异常。
The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes an adenosine 3',5'-monophosphate (cyclic AMP)-activated chloride channel. In cystic fibrosis (CF) patients, loss of CFTR function because of a genetic mutation results in defective cyclic AMP-mediated chloride secretion across epithelia. Because of their potential role as an animal model for CF, mice with targeted disruption of the murine CFTR gene [CFTR(-/-)] were tested for abnormalities in epithelial chloride transport. In both freshly excised tissue from the intestine and in cultured epithelia from the proximal airways, the cyclic AMP-activated chloride secretory response was absent in CFTR(-/-) mice as compared to littermate controls. Thus, disruption of the murine CFTR gene results in the chloride transport abnormalities predicted from studies of human CF epithelia.