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- Title
Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients.
- Authors
Sadakata, Tetsushi; Washida, Miwa; Iwayama, Yoshimi; Shoji, Satoshi; Sato, Yumi; Ohkura, Takeshi; Katoh-Semba, Ritsuko; Nakajima, Mizuho; Sekine, Yukiko; Tanaka, Mika; Nakamura, Kazuhiko; Iwata, Yasuhide; Tsuchiya, Kenji J; Mori, Norio; Detera-Wadleigh, Sevilla D; Ichikawa, Hironobu; Itohara, Shigeyoshi; Yoshikawa, Takeo; Furuichi, Teiichi
- Abstract
Autism, characterized by profound impairment in social interactions and communicative skills, is the most common neurodevelopmental disorder, and its underlying molecular mechanisms remain unknown. Ca(2+)-dependent activator protein for secretion 2 (CADPS2; also known as CAPS2) mediates the exocytosis of dense-core 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.
- Publication
The Journal of clinical investigation, 2007, Vol 117, Issue 4, p931
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI29031