Dataset Information

Whole-Genome Sequencing of Inbred Mouse Strains Selected for High and Low Open-Field Activity.

ABSTRACT: We conducted whole-genome sequencing of four inbred mouse strains initially selected for high (H1, H2) or low (L1, L2) open-field activity (OFA), and then examined strain distribution patterns for all DNA variants that differed between their BALB/cJ and C57BL/6J parental strains. Next, we assessed genome-wide sharing (3,678,826 variants) both between and within the High and Low Activity strains. Results suggested that about 10% of these DNA variants may be associated with OFA, and clearly demonstrated its polygenic nature. Finally, we conducted bioinformatic analyses of functional genomics data from mouse, rat, and human to refine previously identified quantitative trait loci (QTL) for anxiety-related measures. This combination of sequence analysis and genomic-data integration facilitated refinement of previously intractable QTL findings, and identified possible genes for functional follow-up studies.

SUBMITTER: Thomas AL

PROVIDER: S-EPMC7854991 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Whole-Genome Sequencing of Inbred Mouse Strains Selected for High and Low Open-Field Activity.

Thomas Aimee L AL Evans Luke M LM Nelsen Michaela D MD Chesler Elissa J EJ Powers Matthew S MS Booher Winona C WC Lowry Christopher A CA DeFries John C JC Ehringer Marissa A MA

Behavior genetics 20200916 1

We conducted whole-genome sequencing of four inbred mouse strains initially selected for high (H1, H2) or low (L1, L2) open-field activity (OFA), and then examined strain distribution patterns for all DNA variants that differed between their BALB/cJ and C57BL/6J parental strains. Next, we assessed genome-wide sharing (3,678,826 variants) both between and within the High and Low Activity strains. Results suggested that about 10% of these DNA variants may be associated with OFA, and clearly demons ...[more]

PMID: 32939625

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Project description:Open-field activity is a commonly used measure of anxiety-related behavior in rodents. The inbred High and Low Activity strains of mice, selected for extreme differences in open-field activity, have been used as a genetic model of anxiety-related behaviors. These selected strains have been thoroughly studied through extensive behavioral testing, quantitative trait locus (QTL) mapping, whole-genome sequencing, and RNA sequencing, to uncover phenotypic and genotypic differences related to anxiety-related behavior. However, the effects of anxiolytic drugs on anxiety-related behavior in these strains have not been studied previously. This study allowed us to expand on previous findings to further characterize the anxiety-related behavior of these unique strains, using an anxiolytic drug. The goal of this study was to determine whether the treatment of adult male and female High Activity (low anxiety) and Low Activity (high anxiety) mice with diazepam, an agonist at the benzodiazepine allosteric site on the GABAA receptor and a drug commonly prescribed to treat anxiety disorders in humans, led to decreases in anxiety-like defensive behavioral responses as assessed in the open-field test (OFT) and elevated plus-maze (EPM). We tested the effects of three doses of diazepam (0, 0.5, 1.0, 3.0 mg/kg, i.p.), given 30 min before behavioral testing to one High Activity strain (H2) and two Low Activity strains (L1 and L2). There was an anxiolytic effect of diazepam observed in the High Activity strain, with more entries into the open arms of the elevated plus-maze, an effect similar to that seen in common mouse strains. However, the only anxiolytic effect of diazepam seen in the Low Activity strains was a reduction in stretch attend posture (SAP). Low Activity strains also displayed freezing behavior in both the OFT and EPM. The combination of the observed freezing behavior, that was not reduced by diazepam, and the reduction in SAP seen with diazepam, suggests a more complex phenotype that includes a component of innate fear in addition to anxiety-related risk assessment behaviors. Since fear and anxiety are distinguishable traits, and both contribute to human anxiety disorders, these results provide novel insight about interpretation of previous genetic and phenotypic differences observed between the High and Low Activity strains.

Dataset Information

Whole-Genome Sequencing of Inbred Mouse Strains Selected for High and Low Open-Field Activity.

Publications

Whole-Genome Sequencing of Inbred Mouse Strains Selected for High and Low Open-Field Activity.

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