title: Transcriptomic analysis of the hippocampus from six inbred strains of mice suggests a basis for sex-specific susceptibility and severity of neurological disorders.
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.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, 32306.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Vied
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, 32306.|Department of Computer Science, Florida State University, Tallahassee, Florida, 32306.
authors.forename: Surjyendu
authors.initials: S
authors.lastname: Ray
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, 32306.
authors.forename: Crystal-Dawn
authors.initials: CD
authors.lastname: Badger
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, 32306.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Bundy
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, 32306.|Center for Genomics and Personalized Medicine, Florida State University, Tallahassee, Florida, 32306.
authors.forename: Michelle N
authors.initials: MN
authors.lastname: Arbeitman
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, 32306.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Nowakowski
mesh_terms: D000818:Animals; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D053263:Gene Regulatory Networks / Q000235:genetics; D006624:Hippocampus / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology; D012720:Severity of Illness Index; D012727:Sex Characteristics; D013045:Species Specificity
keywords: RRID:IMSR_JAX:000646; RRID:IMSR_JAX:000664; RRID:IMSR_JAX:000670; RRID:IMSR_JAX:000671; RRID:IMSR_JAX:002448; RRID:IMSR_JAX:004660; RRID:OMICS_01043; RRID:OMICS_01097; RRID:OMICS_01257; RRID:OMICS_01304; RRID:OMICS_01306; RRID:OMICS_01938; RRID:nif-0000-21234; RRID:nif-0000-30622; RRID:nif-0000-30654; RRID:nlx_149159; RRID:nlx_149332; RRID:nlx_154607; RRID:nlx_80425; hippocampus; sex differences; transcriptomics