Evaluation of Pax6 Mutant Rat as a Model for Autism
Open accessAbstract
Autism is a highly variable brain developmental disorder and has a strong genetic basis. Pax6 is a pivotal player in brain development and maintenance. It is expressed in embryonic and adult neural stem cells, in astrocytes in the entire central nervous system, and in neurons in the olfactory bulb, amygdala, thalamus, and cerebellum, functioning in highly context-dependent manners. We have recently reported that Pax6 heterozygous mutant (rSey(2)/+) rats with a spontaneous mutation in the Pax6 gene, show impaired prepulse inhibition (PPI). In the present study, we further examined behaviors of rSey(2)/+ rats and revealed that they exhibited abnormality in social interaction (more aggression and withdrawal) in addition to impairment in rearing activity and in fear-conditioned memory. Ultrasonic vocalization (USV) in rSey(2)+ rat pups was normal in male but abnormal in female. Moreover, treatment with clozapine successfully recovered the defects in sensorimotor gating function, but not in fear-conditioned memory. Taken together with our prior human genetic data and results in other literatures, rSey(2)/+ rats likely have some phenotypic components of autism.
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Behavioral analyses of IB2 and Pax6 animal models indicate a possible link between these genes and autistic-like behavior.
“Behavioral analyses of both IB2 and Pax6 animal models have also indicated a possible link between these genes and autistic-like behavior [277, 279].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [279]
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Consensus Paper: Pathological Role of the Cerebellum in Autism
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- Authors
- Umeda, T., Takashima, N., Nakagawa, R., Maekawa, M., Ikegami, S., Yoshikawa, T., Kobayashi, K., Okanoya, K., Inokuchi, K., & Osumi, N.
- Affiliations
- Tohoku University (JP)
- RIKEN Center for Brain Science (JP)
- Saitama Institute of Technology (JP)
- Fukushima Medical University (JP)
- University of Toyama (JP)
- Corresponding author
- Osumi, Noriko
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-12-21
- Volume
- 5
- Issue
- 12
- Pages
- e15500
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3006426
- OpenAlex
- W2045257932
- Cited by
- 70
- References
- 82
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 1 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 3 · 2013: 7 · 2012: 6
- FWCI
- 3.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- autism spectrum disorder, Pax6, spontaneous mutation, prepulse inhibition, sensorimotor gating, social interaction, aggression, ultrasonic vocalizations, clozapine, brain development, neural stem cells, animal models of autism
- MeSH terms
- PAX6 Transcription Factor, Animals, Autistic Disorder, Disease Models, Animal, Eye Proteins, Fear, Female, Male, Memory, Models, Genetic, Mutation, Phenotype, Repressor Proteins, Stem Cells, Ultrasonics, Vocalization, Animal, Homeodomain Proteins, Animals, Genetically Modified, Mice, Rats, Paired Box Transcription Factors
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