Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients
Copyright policy )Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients
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.
- National Institutes of Health United States
- National Institute of Mental Health United States
- RIKEN Brain Science Institute Japan
- Aichi Human Service Center Japan
- Hamamatsu University School of Medicine Japan
Chromosome Aberrations, Mice, Knockout, Cell Death, Calcium-Binding Proteins, Vesicular Transport Proteins, Alternative Splicing, Disease Models, Animal, Mice, Purkinje Cells, Animals, Humans, Female, Genetic Predisposition to Disease, Autistic Disorder, Cognition Disorders, Maternal Behavior, Sequence Deletion
Chromosome Aberrations, Mice, Knockout, Cell Death, Calcium-Binding Proteins, Vesicular Transport Proteins, Alternative Splicing, Disease Models, Animal, Mice, Purkinje Cells, Animals, Humans, Female, Genetic Predisposition to Disease, Autistic Disorder, Cognition Disorders, Maternal Behavior, Sequence Deletion
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).186 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!