Characterization of the human beta4 nAChR gene and polymorphisms in CHRNA3 and CHRNB4.
Characterization of the human beta4 nAChR gene and polymorphisms in CHRNA3 and CHRNB4.
复制标题
人类 beta4 nAChR 基因的表征以及 CHRNA3 和 CHRNB4 的多态性。
DOI：
10.1007/pl00010921
复制
发表时间：
2001
影响因子：
3.5
通讯作者：
Beaudet,AL
中科院分区：
文献类型：
--
作者：
Lev-Lehman,E;Bercovich,D;Xu,W;Stockton,DW;Beaudet,AL
Most neuronal nicotinic acetylcholine receptors are heteropentamers, composed of α and β subunits. Mice lacking the α3 subunit and mice lacking both the β2 and β4 subunits, but not mice lacking the β2 or β4 subunits alone, have a severe phenotype characterized by megacystis, failure of bladder strips to contract in response to nicotine, widely dilated ocular pupils, growth failure, and perinatal mortality. The deficit in bladder contraction was also found in mice lacking only the β4 subunit, although they did not develop megacystis. The major bladder phenotype resembles the human autosomal recessive disorder of megacystis-microcolon-hypoperistalsis syndrome (MMIHS). Based on the similarity of the mouse and human phenotypes, we initiated mutation analyses in the α3 and β4 genes in MMIHS families. The human gene encoding the β4 subunit was fully characterized, including refinement of its mapping. Analysis of disease families and controls identified numerous genetic variants, including high-frequency polymorphisms in both CHRNA3 and CHRNB4. Although no loss-of-function mutations have been identified to date, these genes remain strong candidates for involvement in MMIHS, because various mutations might be obscured within the complex cluster of genes. Some of the markers presented here are valuable tools for analysis of the role of genetic variation in responses to nicotine and for characterization of various dysautonomic abnormalities.
