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Phenotypic and Gene Expression Features Associated with Variation in Chronic Ethanol Consumption in Heterogeneous Stock Collaborative Cross Mice

ABSTRACT: Of the more than 100 studies that have examined some aspect of the relationships between excessive ethanol consumption and the brain transcriptome, relatively few rodent studies have examined the effects of chronic consumption. The current study allowed 114 heterogeneous stock collaborative cross mice to freely consume 10% ethanol for 3 months (13 weeks), with a water choice. RNA-Seq data were then used to identify transcriptional differences within the central nucleus of the amygdala, a brain region known to impact ethanol preference. Average week 1 preference for consuming ethanol over water was modestly correlated with average preference for the final week of the study, and over the course of the 3-month trial, a sex-difference emerged. In females but not males, there was a significant escalation of preference from week 1 to week 13 and significant alignment of the transcriptome with average week 13 ethanol preference and consumption was found for female, but not male mice. The genes significantly correlated with preference were enriched in annotations associated with cilium movement, cilium organization, extracellular region and collagen-containing extracellular matrix. For the females, 376 of the total 415 genes that correlated with ethanol preference in the gene co-expression network were associated with a single network module that was enriched in genes with an astrocyte annotation. The key hub node in the module was the master regulator, orthodenticle homeobox 2 (Otx2). These data support an important role for the extracellular matrix and primary cilium in individual differences in ethanol preference and consumption in a genetically diverse population of mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE151410 | GEO | 2020/05/29

REPOSITORIES: GEO

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Phenotypic and Gene Expression Features Associated with Variation in Chronic Ethanol Consumption in Heterogeneous Stock Collaborative Cross Mice

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