Kitamura Kunio, Yanazawa Masako, Sugiyama Noriyuki, Miura Hirohito, Iizuka-Kogo Akiko, Kusaka Masatomo, Omichi Kayo, Suzuki Rika, Kato-Fukui Yuko, Kamiirisa Kyoko, Matsuo Mina, Kamijo Shin-ichi, Kasahara Megumi, Yoshioka Hidefumi, Ogata Tsutomu, Fukuda Takayuki, Kondo Ikuko, Kato Mitsuhiro, Dobyns William B, Yokoyama Minesuke, Morohashi Ken-ichirou
Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan.
Nat Genet. 2002 Nov;32(3):359-69. doi: 10.1038/ng1009. Epub 2002 Oct 15.
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.
X连锁无芒相关同源盒基因（Arx）发生突变的雄性胚胎小鼠，由于前脑增殖受抑制和区域缺陷而出现脑发育过小的情况。这些小鼠还表现出神经节隆起和新皮质中含γ-氨基丁酸的中间神经元（γ-氨基丁酸能中间神经元）的迁移和分化异常，以及睾丸分化异常。这些特征概括了人类X连锁无脑回畸形伴生殖器异常（XLAG）的一些临床特征。我们在受XLAG影响的个体及其一些女性亲属中发现了ARX的多个功能丧失突变，并得出结论，ARX突变导致XLAG。据我们所知，本报告首次利用基因敲除小鼠的表型分析来鉴定与X连锁人类脑畸形相关的基因。
