Complex Interactions between Genes and Social Environment Cause Phenotypes Associated with Autism Spectrum Disorders in Mice

eNeuro. 2020 Aug 10;7(4):ENEURO.0124-20.2020. doi: 10.1523/ENEURO.0124-20.2020. Print 2020 Jul/Aug.

Abstract

The etiology of autism spectrum disorders (ASDs) is a complex combination of genetic and environmental factors. Neuroligin3, a synaptic adhesion protein, and cytoplasmic FMR1 interacting protein 1 (CYFIP1), a regulator of protein translation and actin polymerization, are two proteins associated with ASDs that interact in neurons in vivo Here, we investigated the role of the Neuroligin3/CYFIP1 pathway in behavioral functioning and synapse formation in mice and found that it contributes to motor learning and synapse formation in males. Similar investigation in female mice revealed an absence of such phenotypes, suggesting that females are protected against mutations affecting this pathway. Previously, we showed that the social environment influences the behavior of male mice. We extended this finding and found that the transcriptome of wild-type mice housed with their mutant littermates, lacking Neuroligin3, differed from the transcriptome of wild-type mice housed together. Altogether, these results identify the role of the Neuroligin3/CYFIP1 pathway in male mouse behavior and highlight its sensitivity to social environment.

Keywords: autism spectrum disorders; motor learning; mouse behavior; social environment.

MeSH terms

  • Animals
  • Autism Spectrum Disorder* / genetics
  • Disease Models, Animal
  • Female
  • Fragile X Mental Retardation Protein
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons
  • Phenotype
  • Social Behavior
  • Social Environment

Substances

  • Fmr1 protein, mouse
  • Fragile X Mental Retardation Protein