細胞分化（諸橋研究室）より，２００２年11月号のNature Geneticsに論文が発表されました。本研究は三菱生命研（北村部長），国立成育医療センター研究所（緒方部長），愛媛大学（近藤教授），シカゴ大（Dobyns 教授），兵庫教育大（吉岡助教授）との共同研究によるものです。

タイトル
Mutation of ARX causes abnormal development of forebrain and
testes in mice and X-linked lissencephaly with abnormal genitalia in humans

著者
Kunio Kitamura. Masako Yanazawa. Noriyuki Sugiyama. HirohitoMiura. Akiko Iizuka-Kogo. Masatomo Kusaka. Kayo Omichi. Rika Suzuki. Yuko Kato-Fukui. Kyoko Kamiirisa. Mina Matsuo. Shin-ichi Kamijo. Megumi Kasahara. Hidefumi Yoshioka. Tsutomu Ogata. Takayuki Fukuda. Ikuko Kondo. Mitsuhiro Kato. William B. Dobyns. Minesuke Yokoyama & Ken-ichirou Morohashi

内容
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-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.