title: Evaluation of Pax6 mutant rat as a model for autism.
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.
authors.affiliation: Division of Developmental Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Umeda
authors.forename: Noriko
authors.initials: N
authors.lastname: Takashima
authors.forename: Ryoko
authors.initials: R
authors.lastname: Nakagawa
authors.forename: Motoko
authors.initials: M
authors.lastname: Maekawa
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegami
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Okanoya
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inokuchi
authors.forename: Noriko
authors.initials: N
authors.lastname: Osumi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001321:Autistic Disorder / Q000235:genetics*; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics*; D005239:Fear; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D008297:Male; D008568:Memory; D051379:Mice; D008957:Models, Genetic; D009154:Mutation; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010641:Phenotype; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology; D014465:Ultrasonics; D014828:Vocalization, Animal
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; C000605733:Pax6 protein, rat; D012097:Repressor Proteins