Transcriptomic analysis of the hippocampus from six inbred strains of mice suggests a basis for sex‐specific susceptibility and severity of neurological disorders. Issue 13 (29th March 2016)

• Record Type: Journal Article
• Authors: Vied, Cynthia; Ray, Surjyendu; Badger, Crystal‐Dawn; Bundy, Joseph L.; Arbeitman, Michelle N.; Nowakowski, Richard S.
• Is Part Of: Journal of comparative neurology. Volume 524:Issue 13(2016)
• Page Start: 2696
• Page End: 2710
• Publication Date: 2016-03-29
• Subjects: hippocampus -- transcriptomics -- sex differences -- RRID:IMSR_JAX:002448 -- RRID:IMSR_JAX:000646 -- RRID:IMSR_JAX:000664 -- RRID:IMSR_JAX:000670 -- RRID:IMSR_JAX:000671 -- RRID:IMSR_JAX:004660 -- RRID:OMICS_01043 -- RRID:OMICS_01097 -- RRID:OMICS_01257 -- RRID:nlx_154607 -- RRID:OMICS_01938 -- RRID:OMICS_01306 -- RRID:OMICS_01304 -- RRID:nif‐0000‐30654 -- RRID:nif‐0000‐30622 -- RRID:nlx_80425 -- RRID:nif‐0000‐21234 -- RRID:nlx_149332 -- RRID:nlx_149159; Comparative neurobiology -- Periodicals; Neurology -- Periodicals; 616
• DOI: 10.1002/cne.23989
• Languages: English
• ISSNs: 0021-9967

Abstract

ABSTRACT: Identifying sex differences in gene expression within the brain is critical for determining why multiple neurological and behavioral disorders differentially affect males and females. Several disorders are more common or severe in males (e.g., autism and schizophrenia) or in females (e.g., Alzheimer's disease and depression). We analyzed transcriptomic data from the mouse hippocampus of six inbred strains (129S1/SvImJ, A/J, C57BL/6J, DBA/1J, DBA/2J, and PWD/Ph) to provide a perspective on differences between male and female gene expression. Our data show that 1) gene expression differences in males vs. females varies substantially across the strains, 2) only a few genes are differentially expressed across all of the strains (termed core genes ), and 3) >2, 600 genes differ in the individual strain comparisons (termed noncore genes ). We found that DBA/2J uniquely has a substantial majority (89%) of differentially expressed genes (DEGs) that are more highly expressed in females than in males (female‐biased); 129/SvImJ has a majority (69%) of DEGs that are more highly expressed in males. To gain insight into the function of the DEGs, we examined gene ontology and pathway and phenotype enrichment and found significant enrichment in phenotypes related to abnormal nervous system morphology and physiology, among others. In addition, several pathways are enriched significantly, including Alzheimer's disease (AD), with 32 genes implicated in AD, eight of which are male‐biased. Three of the male‐biased genes have been implicated in a neuroprotective role in AD. Our transcriptomic data provide new insight into the possible genetic bases for sex‐specific susceptibility and severity of brain disorders. J. Comp. Neurol. 524:2696–2710, 2016. © 2016 Wiley Periodicals, Inc. Abstract : We have examined sex differences in gene expression in the hippocampus of six strains of mice and have found that sex differences exist and that these differences vary substantially among the different strains of mice. Some genes that are different between males and females have been implicated in underlying neurological disorders.