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

Molecular Autism

卷:8

Travis M. Kerr¹  Jing Wang²  Allison M. J. Anacker³  Tiffany D. Rogers⁴  Jeremy Veenstra-VanderWeele⁵  Bing Zhang⁵  C. Gunnar Forsberg⁶ 

[1] New York State Psychiatric Institute;

[2] College of Medicine, Medical University of South Carolina;

[3] Department of Psychiatry, Columbia University;

[4] Department of Psychiatry, Vanderbilt University;

[5] Lester and Sue Smith Breast Center, Baylor College of Medicine;

[6] The University of Tennessee Health Science Center College of Medicine;

关键词: Fragile X syndrome;    Autism spectrum disorder;    Social behavior;    RNA sequencing;    Amygdala;    Prefrontal cortex;   

DOI  :  10.1186/s13229-017-0148-6

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown