TRANSMEMBRANE MUTATIONS ALTER THE CHANNEL CHARACTERISTICS OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR EXPRESSED IN XENOPUS-OOCYTES
TRANSMEMBRANE MUTATIONS ALTER THE CHANNEL CHARACTERISTICS OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR EXPRESSED IN XENOPUS-OOCYTES
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DOI：
10.1159/000154705
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发表时间：
1994-01-01
影响因子：
--
通讯作者：
GUGGINO, WB
中科院分区：
文献类型：
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作者：
CARROLL, TP;MCINTOSH, I;GUGGINO, WB
我们报告，非洲爪蟾卵母细胞注射野生型囊性纤维化跨膜调节因子（CFTR）RNA表现出cAMP调节的Cl-电流。注射携带R117 H（一种与轻度疾病相关的突变）的CFTR RNA诱导cAMP调节的Cl-电流。R117 H诱导的电流幅度始终低于野生型CFTR表达诱导的电流幅度。用抗CFTR抗体的Western印迹证实，在注射正常或突变形式的CFTR mRNA的卵母细胞中表达蛋白质。野生型和突变型CFTR Cl-通道的单通道开放通道概率的等级顺序为野生型> R117 H。这些数据表明，跨膜区的突变影响CFTR通道特性，并与CF疾病严重程度可能与突变CFTR的cAMP调节的Cl-电导降低相关的假设一致。
We report that Xenopus oocytes injected with wild-type cystic fibrosis transmembrane regulator (CFTR) RNA exhibit cAMP-regulated Cl- currents. Injection of CFTR RNA bearing R117H, a mutation associated with mild disease, induces cAMP-regulated Cl- currents. The magnitudes of the currents induced by R117H were consistently lower than those induced by expression of wild-type CFTR. Western blotting with anti-CFTR antibody confirms that protein was expressed in oocytes injected with either normal or the mutant form of CFTR mRNA. The rank order of single channel open channel probabilities of wild-type and mutant CFTR Cl- channels is wild-type > R117H. These data demonstrate that mutations in the transmembrane region affect CFTR channel properties and are consistent with the hypothesis that CF disease severity may be correlated with reduced cAMP-regulated Cl- conductances of mutant CFTR.