# Project 5: Circadian Rhythms

> **NIH NIH P50** · JACKSON LABORATORY · 2020 · $195,652

## Abstract

PROJECT SUMMARY PROJECT 5 – CIRCADIAN RHYTHMS
Circadian rhythm and sleep disruptions increase the vulnerability for addiction disorders, though the genetics
and molecular mechanisms underlying this association remain poorly understood. Genome-wide and more
targeted single-nucleotide polymorphism (SNP) association studies have revealed significant associations
between circadian gene SNPs and addiction disorders. While circadian mutant mice (single gene mutation)
have been useful for beginning to understand these mechanisms, recent genome-wide approaches strongly
indicate that there are many genes that display circadian oscillation and/or influence the robustness of the
molecular clock. Therefore, a number of genes may have novel roles in the regulation of the molecular clock
and addiction related behaviors. An ideal biological tool for investigating the genetics underlying the
relationships between circadian rhythms and addiction related phenotypes are the Collaborative Cross (CC)
and the Diversity Outbred (DO) mouse populations which are bred and housed at Jackson Labs (JAX). The
DO genome consists of ~45 million unique polymorphisms and allelic combinations, and several million
structural variants, which drives extensive genetic and phenotypic variation. This highly diverse genome is a
powerful system for relatively fast, cost-effective, and high-precision genetic analyses to identify novel genetic
loci underlying complex addiction phenotypes. This project (Project 5) will take advantage of mouse cohorts 1,
2 and 3 described in the center, and from behavioral data generated by the Behavioral Phenotyping Core
associated with projects led by Drs. Jentsch, Chesler, Damaj and Tarantino. These projects will investigate the
genetics underlying behavioral impulsivity, nicotine preference, cocaine sensitization and cocaine self-
administration. We will collect tissue samples from all mice for which behavior is recorded, isolate fibroblasts
and use these cells to measure molecular rhythms across multiple days. We will also determine if genetic
variations in the CC/DO founder strains and CC lead to changes in mouse circadian behavior and include
these data along with the molecular data in a large center-wide correlation, which will take place in the
Integrative Genetics and Genomics Core at JAX. Fibroblasts from DO mice will be used to identify candidate
genetic loci, and we will utilize the Mouse Resources and Validation Core to provide us with iPSC-derived
neurons and mice with specific genetic variations for validation studies. Finally, we will measure rhythms in
core clock genes, input and output gene expression, as well as markers of epigenetic gene regulation in the
suprachiasmatic nucleus (SCN) and other addiction-related brain regions such as the nucleus accumbens
(NAc), ventral tegmental area (VTA) and prefrontal cortex (PFC) in the CC/DO founder lines and ultimately in
variants identified in our large DO screen. Through this unique and collabora...

## Key facts

- **NIH application ID:** 9933854
- **Project number:** 5P50DA039841-05
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Colleen A McClung
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $195,652
- **Award type:** 5
- **Project period:** — → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933854

## Citation

> US National Institutes of Health, RePORTER application 9933854, Project 5: Circadian Rhythms (5P50DA039841-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9933854. Licensed CC0.

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