Document Detail


Functional genomic architecture of predisposition to voluntary exercise in mice: expression QTL in the brain.
MedLine Citation:
PMID:  22466041     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The biological basis of voluntary exercise is complex and simultaneously controlled by peripheral (ability) and central (motivation) mechanisms. The accompanying natural reward, potential addiction, and the motivation associated with exercise are hypothesized to be regulated by multiple brain regions, neurotransmitters, peptides, and hormones. We generated a large (n = 815) advanced intercross line of mice (G(4)) derived from a line selectively bred for increased wheel running (high runner) and the C57BL/6J inbred strain. We previously mapped multiple quantitative trait loci (QTL) that contribute to the biological control of voluntary exercise levels, body weight, and composition, as well as changes in body weight and composition in response to short-term exercise. Currently, using a subset of the G(4) population (n = 244), we examined the transcriptional landscape relevant to neurobiological aspects of voluntary exercise by means of global mRNA expression profiles from brain tissue. We identified genome-wide expression quantitative trait loci (eQTL) regulating variation in mRNA abundance and determined the mode of gene action and the cis- and/or trans-acting nature of each eQTL. Subsets of cis-acting eQTL, colocalizing with QTL for exercise or body composition traits, were used to identify candidate genes based on both positional and functional evidence, which were further filtered by correlational and exclusion mapping analyses. Specifically, we discuss six plausible candidate genes (Insig2, Socs2, DBY, Arrdc4, Prcp, IL15) and their potential role in the regulation of voluntary activity, body composition, and their interactions. These results develop a potential initial model of the underlying functional genomic architecture of predisposition to voluntary exercise and its effects on body weight and composition within a neurophysiological framework.
Authors:
Scott A Kelly; Derrick L Nehrenberg; Kunjie Hua; Theodore Garland; Daniel Pomp
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-03-30
Journal Detail:
Title:  Genetics     Volume:  191     ISSN:  1943-2631     ISO Abbreviation:  Genetics     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-15     Completed Date:  2012-10-22     Revised Date:  2014-04-14    
Medline Journal Info:
Nlm Unique ID:  0374636     Medline TA:  Genetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  643-54     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / metabolism*
Chromosome Mapping
Computational Biology / methods
Gene Expression Profiling
Genomics / methods
Haplotypes
Male
Mice
Mice, Inbred C57BL
Motor Activity / genetics*
Quantitative Trait Loci*
Grant Support
ID/Acronym/Agency:
5T32MH075854-04/MH/NIMH NIH HHS; DK-076050/DK/NIDDK NIH HHS; DK056350/DK/NIDDK NIH HHS; P30 ES010126/ES/NIEHS NIH HHS
Comments/Corrections

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