# Effects of chronic ethanol consumption on the mouse brain transcriptome

> **NIH NIH P60** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $100,900

## Abstract

Project Summary / Abstract
Project P003 focuses on examining the transcriptome in mouse chronically (3 months) self-administering
ethanol in the two-bottle choice procedure (water vs 10% ethanol). Data will be collected in two separate
populations of mice (the HS-CC and DO) derived from the 8 founders of the Collaborative Cross that includes
3 wild-derived strains. More than 90% of the genetic diversity available in Mus musculus is represented in the
HS-CC and DO. The experimental design parallels that of the macaque project (P002); a key goal is to
determine if the transcriptional features associated with excessive ethanol consumption in the mouse and
macaque are similar. Where they are, the mouse model provides an accessible platform to examine the
underlying mechanisms. The proposed project contains 3 specific aims. 1. To examine in HS-CC mice the
relationships between chronic (3 month) ethanol consumption and the brain transcriptome. Data will be
collected in six components of the “addiction” neurocircuit : the shell of the nucleus accumbens, the
dorsolateral striatum, the prelimibic cortex, the dorsolateral orbital cortex, the central nucleus of the amygdala
and the centrally projecting Edinger-Westphal nucleus. Preliminary data have established that in HS-CC mice,
chronic consumption ranges from 1 to 20 g/kg/day, with 25% of the animals consuming > 10 g/kg/day. RNA-
Seq will be used to extract the expression data; gene networks are analyzed using the weighted gene
coexpression network analysis (WGCNA). The goal is to detect hub genes which are highly associated with
consumption; these hubs become targets for validation and manipulation in C001. 2. To use the RNA-Seq data
to examine how chronic ethanol consumption has affected alternative splicing. We approach alternative
splicing from a network perspective and look for splicing hubs. 3. To replicate the experiments and workflows
in Aims 1 and 2 using the Diversity Outcross (DO). The DO like the HS-CC is an outbred version of the
Collaborative Cross but differs significantly in breeding history, number of families that are maintained and the
breeding schemes used to prevent genetic drift Nonetheless, our working hypothesis is that, in the HS-CC and
DO cohorts, there will be common (and unique) transcriptional correlates to chronic ethanol exposure. Project
P003 provides a link to previous iterations of the PARC that focused on risk factors for excessive consumption.
Risk genes in CC mice have been identified (Section 3.2) and we now ask, what are the role(s) of these genes
in sustained excessive consumption? Preliminary data are provided to support the integration of the mouse
and macaque data.

## Key facts

- **NIH application ID:** 9841350
- **Project number:** 5P60AA010760-25
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** ROBERT J. HITZEMANN
- **Activity code:** P60 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $100,900
- **Award type:** 5
- **Project period:** — → 2021-02-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841350

## Citation

> US National Institutes of Health, RePORTER application 9841350, Effects of chronic ethanol consumption on the mouse brain transcriptome (5P60AA010760-25). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9841350. Licensed CC0.

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