Sequence and localization of a partial cDNA encoding the human alpha 3 chain of type IV collagen.
Sequence and localization of a partial cDNA encoding the human alpha 3 chain of type IV collagen.
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DOI：
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发表时间：
1991-09
影响因子：
9.8
通讯作者：
K. Morrison;M. Mariyama;T. Yang-Feng;S. Reeders
中科院分区：
文献类型：
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作者：
K. Morrison;M. Mariyama;T. Yang-Feng;S. Reeders
最近在人和牛的基底膜中发现了一种新的IV型胶原，即α3(IV)。在这里，我们描述了编码人α3(IV)链NC1区218个残基的cDNA的克隆和测序。令人感兴趣的是Alport综合征患者基底膜中α3(IV)链异常的可能作用，如未能检测到Alport综合征患者基底膜中的Alpha 3(IV)的NC1域。为了确定Alport综合征是否存在α3(IV)基因(Col4A3)突变，我们通过体细胞杂交分析和中期染色体原位杂交将其定位于染色体2q35-2q37。因此，阿尔波特综合征的绝大多数病例不可能与阿尔法3(IV)的突变有关，这些病例已被证明与X连锁。对Alport综合征发病机制中α3(IV)的免疫化学数据的一种解释是，定位于Xq22的Alpha 5(IV)链的突变导致Alport综合征不能稳定地将Alpha 3(IV)链整合到肾小球基底膜的多聚体结构中。
A novel type IV collagen, alpha 3(IV), has recently been identified in human and bovine basement membranes. Here we describe the cloning and sequencing of a cDNA encoding 218 residues of the NC1 domain of the human alpha 3(IV) chain. Of interest is the possible role of abnormalities of the alpha 3(IV) chain in Alport syndrome, as suggested by the failure to detect the NC1 domain of alpha 3(IV) in the basement membranes of some Alport syndrome patients. To determine whether the alpha 3(IV) gene (COL4A3) may be mutated in Alport syndrome, we localized it, by somatic cell hybrid analysis and in situ hybridization of metaphase chromosomes, to chromosome 2q35-2q37. Mutations in alpha 3(IV) cannot therefore be responsible for the vast majority of cases of Alport syndrome, which have been shown to be X linked. One explanation for the immunochemical data implicating alpha 3(IV) in Alport syndrome pathogenesis is that mutations of the alpha 5(IV) chain, which has been localized to Xq22 and found to be mutated in at least three kindreds with Alport syndrome, lead to failure to incorporate the alpha 3(IV) chains into the multimeric structure of glomerular basement membrane in a stable fashion.