Unknown,Transcriptomics,Genomics,Proteomics

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Effects of selection for ethanol preference on gene expression (RNA-Seq) in the nucleus accumbens shell of HS-CC mice

ABSTRACT: Nucleus accumbens shell gene expression was assessed by RNA-Seq to determine effects of bidirectional selection for ethanol preference from a highly genetically diverse founder population. We analyzed the data with both standard methodologies to detect differential expression, and coexpression network changes, and with novel methodologies to detect alternative exon usage, and coordinated splicing pattern changes due to selection. 48 samples of HSCC animals selected for high and low ethanol preference were analyzed (selection generation 4): 24 females (12 High, 12 Low) 24 males (12 High, 12 Low).

ORGANISM(S): Mus musculus

SUBMITTER: Alexandre Colville

PROVIDER: E-GEOD-65950 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Purpose: Genetic factors significantly affect alcohol consumption and vulnerability to withdrawal. Some genetic models that show predisposition to severe withdrawal are also predisposed to low ethanol consumption and vice versa, even when tested independently in naïve animals. The study was undertaken to understand gene and network differences between mice selectively bred for high withdrawal/low withdrawal or low withdrawal/high consumption. Methods: Beginning with a C57BL/6J×DBA/2J F2 intercross founder population, animals were simultaneously selectively bred for both high alcohol consumption and low acute withdrawal (SOT line), or vice versa (NOT line). Using randomly chosen fourth selected generation (S4) mice (N= 18-22/sex/line), RNA-Seq was employed to assess genome-wide gene expression in the ventral striatum. The Mega-MUGA array was used to detect genome-wide genotypic differences. Differential gene expression and the weighted gene co-expression network analysis (WGCNA) were implemented. Results: The new selection of the SOT and NOT lines was similar to that reported previously (Metten et al. 2014). One thousand eight hundred and fifteen transcripts were detected as being differentially expressed between the lines. For the genes overexpressed in the SOT line there was enrichment in genes associated with cell adhesion, synapse organization and post-synaptic membrane. The genes with a cell adhesion annotation included 23 protocadherins, Mpdz & Dlg2. Genes with a postsynaptic membrane annotation included Gabrb3, Gphn, Grid1, Grin2b, Grin2c & Grm3. The genes overexpressed in the NOT line were enriched in a network module (red) with annotations associated with mitochondrial function. Several of these genes were module hub nodes and these included Nedd8, Guk1, Elof1, Ndufa8, & Atp6v1f. Conclusions: Marked effects of selection on gene expression were detected. The NOT line was characterized by the increased expression of hub nodes associated with mitochondrial function. Genes overexpressed in the SOT aligned with previous findings e.g. Colville et al. (2017) that high ethanol preference and consumption is associated with effects on cell adhesion and glutamate synaptic plasticity.

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Effects of selection for ethanol preference on gene expression (RNA-Seq) in the nucleus accumbens shell of HS-CC mice

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