2. Academic Validation
  3. 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

  • Nat Genet. 2002 Nov;32(3):359-69. doi: 10.1038/ng1009.
Kunio Kitamura 1,  Masako Yanazawa,  Noriyuki Sugiyama,  Hirohito Miura,  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
Affiliations

Affiliation

  • 1 Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan. kunio@libra.ls.m-kagaku.co.jp
PMID: 12379852 DOI: 10.1038/ng1009
Abstract

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.

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