title: Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients.
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.
authors: Laboratory for Molecular Neurogenesis and Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors: Tetsushi
authors: T
authors: Sadakata
authors: Miwa
authors: M
authors: Washida
authors: Yoshimi
authors: Y
authors: Iwayama
authors: Satoshi
authors: S
authors: Shoji
authors: Yumi
authors: Y
authors: Sato
authors: Takeshi
authors: T
authors: Ohkura
authors: Ritsuko
authors: R
authors: Katoh-Semba
authors: Mizuho
authors: M
authors: Nakajima
authors: Yukiko
authors: Y
authors: Sekine
authors: Mika
authors: M
authors: Tanaka
authors: Kazuhiko
authors: K
authors: Nakamura
authors: Yasuhide
authors: Y
authors: Iwata
authors: Kenji J
authors: KJ
authors: Tsuchiya
authors: Norio
authors: N
authors: Mori
authors: Sevilla D
authors: SD
authors: Detera-Wadleigh
authors: Hironobu
authors: H
authors: Ichikawa
authors: Shigeyoshi
authors: S
authors: Itohara
authors: Takeo
authors: T
authors: Yoshikawa
authors: Teiichi
authors: T
authors: Furuichi
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001321:Autistic Disorder / Q000235:genetics* / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D016923:Cell Death; D002869:Chromosome Aberrations; D003072:Cognition Disorders / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008425:Maternal Behavior; D051379:Mice; D018345:Mice, Knockout; D011689:Purkinje Cells / Q000473:pathology; D017384:Sequence Deletion; D033921:Vesicular Transport Proteins / Q000172:deficiency / Q000235:genetics*
chemical_list: C479428:CADPS2 protein, human; D002135:Calcium-Binding Proteins; D033921:Vesicular Transport Proteins