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Gestational immune activation and Tsc2 haploinsufficiency cooperate to disrupt fetal survival and may perturb social behavior in adult mice

A Corrigendum to this article was published on 26 March 2012

Abstract

Approximately 40–50% of individuals affected by tuberous sclerosis (TSC) develop autism spectrum disorders (ASDs). One possible explanation for this partial penetrance is an interaction between TSC gene mutations and other risk factors such as gestational immune activation. In this study, we report the interactive effects of these two ASD risk factors in a mouse model of TSC. Combined, but not single, exposure had adverse effects on intrauterine survival. Additionally, provisional results suggest that these factors synergize to disrupt social approach behavior in adult mice. Moreover, studies in human populations are consistent with an interaction between high seasonal flu activity in late gestation and TSC mutations in ASD. Taken together, our studies raise the possibility of a gene × environment interaction between heterozygous TSC gene mutations and gestational immune activation in the pathogenesis of TSC-related ASD.

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Acknowledgements

We thank Paul H Patterson and Steven E Smith for valuable input regarding the gestational immune activation paradigm. This work was supported by funds of the German Center for Neurodegenerative Diseases to DE, the NIH R01 MH084315 to AJS and a grant from the Children's Hospital Boston Translational Research Program to MS.

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Correspondence to D Ehninger or A J Silva.

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Ehninger, D., Sano, Y., de Vries, P. et al. Gestational immune activation and Tsc2 haploinsufficiency cooperate to disrupt fetal survival and may perturb social behavior in adult mice. Mol Psychiatry 17, 62–70 (2012). https://doi.org/10.1038/mp.2010.115

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Keywords

  • tuberous sclerosis
  • TCS2
  • poly I:C
  • gestational immune activation
  • autism
  • ASD
  • behavior

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