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PloS one
Dec 21, 2010;5 (12): e15500.

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
Author Information
  1. Toshiko Umeda: Division of Developmental Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan.
PMID: 21203536 DOI: 10.1371/journal.pone.0015500

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 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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MeSH Term

Animals
Animals, Genetically Modified
Autistic Disorder
Disease Models, Animal
Eye Proteins
Fear
Female
Homeodomain Proteins
Male
Memory
Mice
Models, Genetic
Mutation
PAX6 Transcription Factor
Paired Box Transcription Factors
Phenotype
Rats
Repressor Proteins
Stem Cells
Ultrasonics
Vocalization, Animal

Chemicals

Eye Proteins
Homeodomain Proteins
PAX6 Transcription Factor
PAX6 protein, human
Paired Box Transcription Factors
Pax6 protein, mouse
Pax6 protein, rat
Repressor Proteins
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 2

Word Cloud

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