Comprehensive Profiling of Gene Expression in the Cerebral Cortex and Striatum of BTBRTF/ArtRbrc Mice Compared to C57BL/6J Mice

Shota Mizuno; Jun-na Hirota; Chiaki Ishii; Hirohide Iwasaki; Yoshitake Sano; Teiichi Furuichi

doi:10.3389/fncel.2020.595607

Frontiers in Cellular Neuroscience (Dec 2020)

Comprehensive Profiling of Gene Expression in the Cerebral Cortex and Striatum of BTBRTF/ArtRbrc Mice Compared to C57BL/6J Mice

Shota Mizuno,
Jun-na Hirota,
Chiaki Ishii,
Hirohide Iwasaki,
Yoshitake Sano,
Teiichi Furuichi

Affiliations

Shota Mizuno: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Japan
Jun-na Hirota: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Japan
Chiaki Ishii: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Japan
Hirohide Iwasaki: Department of Anatomy, Gunma University Graduate School of Medicine, Maebashi, Japan
Yoshitake Sano: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Japan
Teiichi Furuichi: Department of Applied Biological Science, Faculty of Science and Technology, Tokyo University of Science, Noda, Japan

DOI: https://doi.org/10.3389/fncel.2020.595607
Journal volume & issue: Vol. 14

Abstract

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Mouse line BTBR T+ Iptr3tf/J (hereafter referred as to BTBR/J) is a mouse strain that shows lower sociability compared to the C57BL/6J mouse strain (B6) and thus is often utilized as a model for autism spectrum disorder (ASD). In this study, we utilized another subline, BTBRTF/ArtRbrc (hereafter referred as to BTBR/R), and analyzed the associated brain transcriptome compared to B6 mice using microarray analysis, quantitative RT-PCR analysis, various bioinformatics analyses, and in situ hybridization. We focused on the cerebral cortex and the striatum, both of which are thought to be brain circuits associated with ASD symptoms. The transcriptome profiling identified 1,280 differentially expressed genes (DEGs; 974 downregulated and 306 upregulated genes, including 498 non-coding RNAs [ncRNAs]) in BTBR/R mice compared to B6 mice. Among these DEGs, 53 genes were consistent with ASD-related genes already established. Gene Ontology (GO) enrichment analysis highlighted 78 annotations (GO terms) including DNA/chromatin regulation, transcriptional/translational regulation, intercellular signaling, metabolism, immune signaling, and neurotransmitter/synaptic transmission-related terms. RNA interaction analysis revealed novel RNA–RNA networks, including 227 ASD-related genes. Weighted correlation network analysis highlighted 10 enriched modules including DNA/chromatin regulation, neurotransmitter/synaptic transmission, and transcriptional/translational regulation. Finally, the behavioral analyses showed that, compared to B6 mice, BTBR/R mice have mild but significant deficits in social novelty recognition and repetitive behavior. In addition, the BTBR/R data were comprehensively compared with those reported in the previous studies of human subjects with ASD as well as ASD animal models, including BTBR/J mice. Our results allow us to propose potentially important genes, ncRNAs, and RNA interactions. Analysis of the altered brain transcriptome data of the BTBR/R and BTBR/J sublines can contribute to the understanding of the genetic underpinnings of autism susceptibility.

Published in Frontiers in Cellular Neuroscience

ISSN: 1662-5102 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: http://www.frontiersin.org/cellular-neuroscience

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