Autistic-like phenotypes in Cadps2-knockout mice and aberrant CADPS2 splicing in autistic patients
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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.
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Canonical ASD mouse models were shown to display a reduction in the number of PV-immunoreactive cells in various brain regions.
“As already reported in several studies [47, 72–74] canonical ASD mouse models were shown to display a reduction in the number of PV-immunoreactive cells in various brain regions.”
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CAPS1 RNA Editing Promotes Dense Core Vesicle Exocytosis
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Environmental Enrichment Induces Epigenomic and Genome Organization Changes Relevant for Cognition
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Position effect leading to haploinsufficiency in a mosaic ring chromosome 14 in a boy with autism
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Bio-collections in autism research
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Lack of stress responses to long-term effects of corticosterone in Caps2 knockout mice
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Triggers for Autism: Genetic and Environmental Factors
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Self-citation
- Authors
- Sadakata, T., Washida, M., Iwayama, Y., Shoji, S., Sato, Y., Ohkura, T., Katoh-Semba, R., Nakajima, M., Sekine, Y., Tanaka, M., Nakamura, K., Iwata, Y., Tsuchiya, K. J., Mori, N., Detera-Wadleigh, S. D., Ichikawa, H., Itohara, S., Yoshikawa, T., & Furuichi, T.
- Affiliations
- RIKEN (JP)
- RIKEN Center for Brain Science (JP)
- Hamamatsu University (JP)
- Corresponding author
- Furuichi, Teiichi
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2007-04-02
- Volume
- 117
- Issue
- 4
- Pages
- 931-943
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1821065
- OpenAlex
- W2081229769
- Cited by
- 218
- References
- 65
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 10 · 2023: 5 · 2022: 12 · 2021: 21 · 2020: 5 · 2019: 10 · 2018: 10 · 2017: 18 · 2016: 11 · 2015: 5 · 2014: 11 · 2013: 8 · 2012: 13
- FWCI
- 8.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (17700322)
- RIKEN
- RIKEN Brain Science Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- autism spectrum disorder, alternative splicing, exon 3 deletion, neurodevelopmental disorders
- MeSH terms
- Animals, Autistic Disorder, Calcium-Binding Proteins, Chromosome Aberrations, Cognition Disorders, Disease Models, Animal, Female, Humans, Maternal Behavior, Purkinje Cells, Cell Death, Sequence Deletion, Alternative Splicing, Mice, Knockout, Genetic Predisposition to Disease, Vesicular Transport Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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