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

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

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1208-1214
Number of pages7
JournalMolecular Psychiatry
Volume21
Issue number9
DOIs
StatePublished - Sep 1 2016

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Structure and function of neonatal social communication in a genetic mouse model of autism'. Together they form a unique fingerprint.

Cite this