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Molecular Autism
Published in: Molecular Autism 1/2017

Open Access 01-12-2017 | Research

Effects of a social stimulus on gene expression in a mouse model of fragile X syndrome

Authors: Tiffany D. Rogers, Allison M. J. Anacker, Travis M. Kerr, C. Gunnar Forsberg, Jing Wang, Bing Zhang, Jeremy Veenstra-VanderWeele

Published in: Molecular Autism | Issue 1/2017

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Abstract

Background

People with fragile X syndrome (FXS) often have deficits in social behavior, and a substantial portion meet criteria for autism spectrum disorder. Though the genetic cause of FXS is known to be due to the silencing of FMR1, and the Fmr1 null mouse model representing this lesion has been extensively studied, the contributions of this gene and its protein product, FMRP, to social behavior are not well understood.

Methods

Fmr1 null mice and wildtype littermates were exposed to a social or non-social stimulus. In one experiment, subjects were assessed for expression of the inducible transcription factor c-Fos in response to the stimulus, to detect brain regions with social-specific activity. In a separate experiment, tissue was taken from those brain regions showing differential activity, and RNA sequencing was performed.

Results

Immunohistochemistry revealed a significantly greater number of c-Fos-positive cells in the lateral amygdala and medial amygdala in the brains of mice exposed to a social stimulus, compared to a non-social stimulus. In the prelimbic cortex, there was no significant effect of social stimulus; although the number of c-Fos-positive cells was lower in the social condition compared to the non-social condition, and negatively correlated with c-Fos in the amygdala. RNA sequencing revealed differentially expressed genes enriched for molecules known to interact with FMRP and also for autism-related genes identified in the Simons Foundation Autism Research Initiative gene database. Ingenuity Pathway Analysis detected enrichment of differentially expressed genes in networks and pathways related to neuronal development, intracellular signaling, and inflammatory response.

Conclusions

Using the Fmr1 null mouse model of fragile X syndrome, we have identified brain regions, gene networks, and molecular pathways responsive to a social stimulus. These findings, and future experiments following up on the role of specific gene networks, may shed light on the neural mechanisms underlying dysregulated social behaviors in fragile X syndrome and more broadly.
Appendix
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Metadata
Title
Effects of a social stimulus on gene expression in a mouse model of fragile X syndrome
Authors
Tiffany D. Rogers
Allison M. J. Anacker
Travis M. Kerr
C. Gunnar Forsberg
Jing Wang
Bing Zhang
Jeremy Veenstra-VanderWeele
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2017
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-017-0148-6

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