title: Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans.
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.
authors.affiliation: Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan. kunio@libra.ls.m-kagaku.co.jp
authors.forename: Kunio
authors.initials: K
authors.lastname: Kitamura
authors.forename: Masako
authors.initials: M
authors.lastname: Yanazawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sugiyama
authors.forename: Hirohito
authors.initials: H
authors.lastname: Miura
authors.forename: Akiko
authors.initials: A
authors.lastname: Iizuka-Kogo
authors.forename: Masatomo
authors.initials: M
authors.lastname: Kusaka
authors.forename: Kayo
authors.initials: K
authors.lastname: Omichi
authors.forename: Rika
authors.initials: R
authors.lastname: Suzuki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kato-Fukui
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kamiirisa
authors.forename: Mina
authors.initials: M
authors.lastname: Matsuo
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kamijo
authors.forename: Megumi
authors.initials: M
authors.lastname: Kasahara
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fukuda
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kondo
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kato
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
authors.forename: Minesuke
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Ken-ichirou
authors.initials: K
authors.lastname: Morohashi
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D001921:Brain / Q000002:abnormalities / Q000473:pathology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement; D018076:DNA, Complementary / Q000378:metabolism; D000089662:Doublecortin Protein; D004847:Epithelial Cells / Q000378:metabolism; D008040:Genetic Linkage; D005822:Genetic Vectors; D005835:Genitalia / Q000002:abnormalities*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D016548:Prosencephalon / Q000002:abnormalities*; D013577:Syndrome; D013737:Testis / Q000002:abnormalities* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D014162:Transfection; D014960:X Chromosome / Q000235:genetics*
chemical_list: C469264:ARX protein, human; C469265:ARX protein, mouse; D018076:DNA, Complementary; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D018398:Homeodomain Proteins; D014157:Transcription Factors; D001973:Bromodeoxyuridine