Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans
Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans
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DOI：
10.1038/ng1009
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发表时间：
2002-11-01
期刊：
影响因子：
30.8
通讯作者：
Morohashi, K
中科院分区：
文献类型：
--
作者：
Kitamura, K;Yanazawa, M;Morohashi, K
在X-连锁aristaless-related同源异型盒基因（Arx）突变的雄性胚胎小鼠，由于增殖抑制和前脑区域缺陷，发育出小大脑。这些小鼠还表现出神经节隆起和新皮质中含有γ-氨基丁酸的中间神经元（GABA能中间神经元）的异常迁移和分化以及异常睾丸分化。这些特征概括了人类X连锁无脑畸形伴生殖器异常（XLAG）的一些临床特征。我们在XLAG患者和一些女性亲属中发现了多个ARX功能缺失突变，并得出结论：ARX突变导致XLAG。本报告是，据我们所知，第一次使用敲除小鼠的表型分析，以确定与X连锁人脑畸形相关的基因。
Male embryonic mice with mutations in the X-linked aristaless-related homeobox gene (Arx) developed with small brains due to suppressed proliferation and regional deficiencies in the forebrain. These mice also showed aberrant migration and differentiation of interneurons containing gamma-aminobutyric acid (GABAergic interneurons) in the ganglionic eminence and neocortex as well as abnormal testicular differentiation. These characteristics recapitulate some of the clinical features of X-linked lissencephaly with abnormal genitalia (XLAG) in humans. We found multiple loss-of-function mutations in ARX in individuals affected with XLAG and in some female relatives, and conclude that mutation of ARX causes XLAG. The present report is, to our knowledge, the first to use phenotypic analysis of a knockout mouse to identify a gene associated with an X-linked human brain malformation.