Structure and function of neonatal social communication in a genetic mouse model of autism

T. Takahashi, S. Okabe, P. Broin, A. Nishi, Qian K. Ye, M. V. Beckert, T. Izumi, A. Machida, G. Kang, S. Abe, Jose L. Pena, A. Golden, T. Kikusui, Noboru Hiroi

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

A critical step toward understanding autism spectrum disorder (ASD) is to identify both genetic and environmental risk factors. A number of rare copy number variants (CNVs) have emerged as robust genetic risk factors for ASD, but not all CNV carriers exhibit ASD and the severity of ASD symptoms varies among CNV carriers. Although evidence exists that various environmental factors modulate symptomatic severity, the precise mechanisms by which these factors determine the ultimate severity of ASD are still poorly understood. Here, using a mouse heterozygous for Tbx1 (a gene encoded in 22q11.2 CNV), we demonstrate that a genetically triggered neonatal phenotype in vocalization generates a negative environmental loop in pup–mother social communication. Wild-type pups used individually diverse sequences of simple and complicated call types, but heterozygous pups used individually invariable call sequences with less complicated call types. When played back, representative wild-type call sequences elicited maternal approach, but heterozygous call sequences were ineffective. When the representative wild-type call sequences were randomized, they were ineffective in eliciting vigorous maternal approach behavior. These data demonstrate that an ASD risk gene alters the neonatal call sequence of its carriers and this pup phenotype in turn diminishes maternal care through atypical social communication. Thus, an ASD risk gene induces, through atypical neonatal call sequences, less than optimal maternal care as a negative neonatal environmental factor.Molecular Psychiatry advance online publication, 15 December 2015; doi:10.1038/mp.2015.190.

Original languageEnglish (US)
JournalMolecular Psychiatry
DOIs
StateAccepted/In press - Dec 15 2015

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Genetic Models
Autistic Disorder
Communication
Mothers
Choice Behavior
Genes
Phenotype
Maternal Behavior
Autism Spectrum Disorder
Psychiatry
Publications

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Structure and function of neonatal social communication in a genetic mouse model of autism. / Takahashi, T.; Okabe, S.; Broin, P.; Nishi, A.; Ye, Qian K.; Beckert, M. V.; Izumi, T.; Machida, A.; Kang, G.; Abe, S.; Pena, Jose L.; Golden, A.; Kikusui, T.; Hiroi, Noboru.

In: Molecular Psychiatry, 15.12.2015.

Research output: Contribution to journalArticle

Takahashi, T, Okabe, S, Broin, P, Nishi, A, Ye, QK, Beckert, MV, Izumi, T, Machida, A, Kang, G, Abe, S, Pena, JL, Golden, A, Kikusui, T & Hiroi, N 2015, 'Structure and function of neonatal social communication in a genetic mouse model of autism', Molecular Psychiatry. https://doi.org/10.1038/mp.2015.190
Takahashi, T. ; Okabe, S. ; Broin, P. ; Nishi, A. ; Ye, Qian K. ; Beckert, M. V. ; Izumi, T. ; Machida, A. ; Kang, G. ; Abe, S. ; Pena, Jose L. ; Golden, A. ; Kikusui, T. ; Hiroi, Noboru. / Structure and function of neonatal social communication in a genetic mouse model of autism. In: Molecular Psychiatry. 2015.
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