Colledge W H, Abella B S, Southern K W, Ratcliff R, Jiang C, Cheng S H, MacVinish L J, Anderson J R, Cuthbert A W, Evans M J
Wellcome/CRC Institute of Cancer and Developmental Biology, University of Cambridge, UK.
Nat Genet. 1995 Aug;10(4):445-52. doi: 10.1038/ng0895-445.
We have generated mice carrying the most common mutation in cystic fibrosis (CF), delta F508, within the cystic fibrosis (Cftr) gene. Mutant animals show pathological and electrophysiological changes consistent with a CF phenotype. delta F508-/- mice die from peritonitis and show deficiencies in cAMP-activated electrogenic Cl- transport. These mice produce delta F508 transcripts and show the temperature-dependent trafficking defect first described for the human delta F508 CFTR protein. A functional CFTR Cl- channel not demonstrated by null CF mice or present at 37 degrees C was detected following incubation of epithelial cells at 27 degrees C. Thus, these mice are an accurate delta F508 model and will be valuable for testing drugs aimed at overcoming the delta F508 trafficking defect.
我们已经培育出了在囊性纤维化跨膜传导调节因子（Cftr）基因中携带囊性纤维化（CF）最常见突变——ΔF508的小鼠。突变动物表现出与CF表型一致的病理和电生理变化。ΔF508基因敲除小鼠死于腹膜炎，并表现出cAMP激活的电致性Cl-转运缺陷。这些小鼠产生ΔF508转录本，并表现出最初在人类ΔF508 CFTR蛋白中描述的温度依赖性转运缺陷。在用上皮细胞在27℃孵育后，检测到了在CF基因敲除小鼠中未表现出或在37℃时不存在的功能性CFTR Cl-通道。因此，这些小鼠是准确的ΔF508模型，对于测试旨在克服ΔF508转运缺陷的药物将具有重要价值。
