Evaluation of pax6 mutant rat as a model for autism

Toshiko Umeda, Noriko Takashima, Ryoko Nakagawa, Motoko Maekawa, Shiro Ikegami, Takeo Yoshikawa, Kazuto Kobayashi, Kazuo Okanoya, Kaoru Inokuchi, Noriko Osumi

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

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 contextdependent manners. We have recently reported that Pax6 heterozygous mutant (rSey2/+) rats with a spontaneous mutation in the Pax6 gene, show impaired prepulse inhibition (PPI). In the present study, we further examined behaviors of rSey2/+ rats and revealed that they exhibited abnormality in social interaction (more aggression and withdrawal) in addition to impairment in earing activity and in fear-conditioned memory. Ultrasonic vocalization (USV) in rSey2+ rat pups was normal in male but abnormal in female. Moreover, treatment with clozapine successfully recovered the defects in ensorimotor gating function, but not in fear-conditioned memory. Taken together with our prior human genetic data and results in other literatures, rSey2/+ rats likely have some phenotypic components of autism.

Original languageEnglish
Article numbere15500
JournalPloS one
Volume5
Issue number12
DOIs
Publication statusPublished - 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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