MISC

2007年4月

Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients

JOURNAL OF CLINICAL INVESTIGATION
  • Tetsushi Sadakata
  • ,
  • Miwa Washida
  • ,
  • Yoshimi Iwayama
  • ,
  • Satoshi Shoji
  • ,
  • Yumi Sato
  • ,
  • Takeshi Ohkura
  • ,
  • Ritsuko Katoh-Semba
  • ,
  • Mizuho Nakajima
  • ,
  • Yukiko Sekine
  • ,
  • Mika Tanaka
  • ,
  • Kazuhiko Nakamura
  • ,
  • Yasuhide Iwata
  • ,
  • Kenji J. Tsuchiya
  • ,
  • Norio Mori
  • ,
  • Sevilla D. Detera-Wadleigh
  • ,
  • Hironobu Ichikawa
  • ,
  • Shigeyoshi Itohara
  • ,
  • Takeo Yoshikawa
  • ,
  • Teiichi Furuichi

117
4
開始ページ
931
終了ページ
943
記述言語
英語
掲載種別
DOI
10.1172/JCI29031
出版者・発行元
AMER SOC CLINICAL INVESTIGATION INC

Autism, characterized by profound impairment in social interactions and communicative skills, is the most common neurodevelopmental disorder, and its underlying molecular mechanisms remain unknown. Ca2+-dependent activator protein for secretion 2 (CADPS2; also known as CAPS2) mediates the exocytosis of densecore vesicles, and the human CADPS2 is located within the autism susceptibility locus 1 on chromosome 7q. Here we show that Cadps2-knockout mice not only have impaired brain-derived neurotrophic factor release but also show autistic-like cellular and behavioral phenotypes. Moreover, we found an aberrant alternatively spliced CADPS2 mRNA that lacks exon 3 in some autistic patients. Exon 3 was shown to encode the dynactin 1-binding domain and affect axonal CADPS2 protein distribution. Our results suggest that a disturbance in CADPS2-mediated neurotrophin release contributes to autism susceptibility.

Web of Science ® 被引用回数 : 122

リンク情報
DOI
https://doi.org/10.1172/JCI29031
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000245451700015&DestApp=WOS_CPL