CFTR-deficient pigs display peripheral nervous system defects at birth.
CFTR-deficient pigs display peripheral nervous system defects at birth.
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CFTR 缺陷的猪在出生时表现出周围神经系统缺陷。
DOI：
10.1073/pnas.1222729110
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发表时间：
2013
影响因子：
11.1
通讯作者：
Welsh,MichaelJ
中科院分区：
文献类型：
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作者：
Reznikov,LeahR;Dong,Qian;Chen,Jeng-Haur;Moninger,ThomasO;Park,JungMin;Zhang,Yuzhou;Du,Jianyang;Hildebrand,MichaelS;Smith,RichardJH;Randak,ChristophO;Stoltz,DavidA;Welsh,MichaelJ
囊性纤维症患者有包括神经病变在内的周围神经系统异常的报道。这些异常很大程度上归因于该病的继发性表现。我们通过对新生−/−猪的研究，验证了囊性纤维化跨膜传导调节基因的破坏直接影响神经系统功能的假说。我们发现CFTR在雪旺细胞中的表达和活性，CFTR的缺失导致超微结构的髓鞘异常，类似于已知的神经疾病。与神经病理变化一致，我们发现髓鞘蛋白零的转录本增加，当突变时，会导致轴突和/或脱髓鞘神经病。此外，轴突密度降低，三叉神经和坐骨神经传导速度减慢。此外，活体听觉脑干诱发电位显示前庭耳蜗神经传导延迟。我们的数据表明CFRR的丢失直接改变了雪旺细胞的功能，囊性纤维症患者的一些神经系统缺陷可能是主要的。
Peripheral nervous system abnormalities, including neuropathy, have been reported in people with cystic fibrosis. These abnormalities have largely been attributed to secondary manifestations of the disease. We tested the hypothesis that disruption of thecystic fibrosis transmembrane conductance regulator(CFTR) gene directly influences nervous system function by studying newbornCFTR−/−pigs. We discovered CFTR expression and activity in Schwann cells, and loss of CFTR caused ultrastructural myelin sheath abnormalities similar to those in known neuropathies. Consistent with neuropathic changes, we found increased transcripts formyelin protein zero, a gene that, when mutated, can cause axonal and/or demyelinating neuropathy. In addition, axon density was reduced and conduction velocities of the trigeminal and sciatic nerves were decreased. Moreover, in vivo auditory brainstem evoked potentials revealed delayed conduction of the vestibulocochlear nerve. Our data suggest that loss ofCFTRdirectly alters Schwann cell function and that some nervous system defects in people with cystic fibrosis are likely primary.