Studies in transgenic mice indicate a loss of connexin32 function in X-linked Charcot-Marie-tooth disease
Studies in transgenic mice indicate a loss of connexin32 function in X-linked Charcot-Marie-tooth disease
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DOI：
10.1097/00005072-199907000-00004
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发表时间：
1999-07-01
影响因子：
3.2
通讯作者：
Fischbeck, KH
中科院分区：
文献类型：
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作者：
Abel, A;Bone, LJ;Fischbeck, KH
X-连锁Charcot-Marie-Tooth病(CMTX)是一种遗传性脱髓鞘神经病，由缝隙连接蛋白32(Cx32)基因突变引起。尽管在Cx32编码序列中发现了160多种不同的突变，但尚不清楚这些突变是通过Cx32功能丧失还是通过对周围神经的毒性作用导致疾病表现。我们创造了在密码子175(175fs)处发生移码突变的转基因小鼠，这是在一个大型CMTX家系中发现的。对成年转基因动物的周围神经进行光镜检查，未见病理特征。通过逆转录聚合酶链式反应和核糖核酸酶保护实验检测到转基因信使RNA的表达，但Western blotting未检测到任何一株转基因Cx32蛋白。我们的发现表明，175fs突变导致Cx32功能丧失，没有额外的毒性影响。
X-linked Charcot-Marie-Tooth disease (CMTX) is an inherited demyelinating neuropathy caused by mutations in the gene encoding the gap junction protein connexin32 (Cx32). Despite the identification of over 160 different mutations in the Cx32 coding sequence, it is not known whether the mutations cause the disease manifestations through a loss of Cx32 function or through toxic effects on peripheral nerve. We created transgenic mice with a frameshift mutation at codon 175 (175fs), identified in a large CMTX pedigree. Light microscopic examination of the peripheral nerves from adult transgenic animals showed no pathological features. Western blotting did not show transgenic Cx32 protein in any of the 26 lines, although expression of transgenic messenger RNA was detected by reverse-transcriptase polymerase chain reaction and by ribonuclease protection assay. Our findings indicate that the 175fs mutation results in a loss of Cx32 function, without additional toxic effects.