Apr, 2007
Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients
JOURNAL OF CLINICAL INVESTIGATION
- Volume
- 117
- Number
- 4
- First page
- 931
- Last page
- 943
- Language
- English
- Publishing type
- DOI
- 10.1172/JCI29031
- Publisher
- 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.
- Link information
- ID information
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- DOI : 10.1172/JCI29031
- ISSN : 0021-9738
- eISSN : 1558-8238
- Web of Science ID : WOS:000245451700015