Evaluation of heritable determinants of blood and brain serotonin homeostasis using recombinant inbred mice

R. Ye, A. M.D. Carneiro, D. Airey, E. Sanders-Bush, Robert Williams, Lu Lu, J. Wang, B. Zhang, R. D. Blakely

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The biogenic amine serotonin (5-HT, 5-hydroxytryptamine) exerts powerful, modulatory control over multiple physiological functions in the brain and periphery, ranging from mood and appetite to vasoconstriction and gastrointestinal motility. In order to gain insight into shared and distinct molecular and phenotypic networks linked to variations in 5-HT homeostasis, we capitalized on the stable genetic variation present in recombinant inbred mouse strains. This family of strains, all derived from crosses between C57BL/6J and DBA/2J (BXD) parents, represents a unique, community resource with approximately 40years of assembled phenotype data that can be exploited to explore and test causal relationships in silico. We determined levels of 5-HT and 5-hydroxyindoleacetic acid from whole blood, midbrain and thalamus/hypothalamus (diencephalon) of 38 BXD lines and both sexes. All 5-HT measures proved highly heritable in each region, although both gender and region significantly impacted between-strain correlations. Our studies identified both expected and novel biochemical, anatomical and behavioral phenotypes linked to 5-HT traits, as well as distinct quantitative trait loci. Analyses of these loci nominate a group of genes likely to contribute to gender- and region-specific capacities for 5-HT signaling.

Original languageEnglish (US)
Pages (from-to)247-260
Number of pages14
JournalGenes, Brain and Behavior
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2014

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Serotonin
Homeostasis
Brain
Phenotype
Diencephalon
Inbred Strains Mice
Hydroxyindoleacetic Acid
Gastrointestinal Motility
Biogenic Amines
Quantitative Trait Loci
Appetite
Mesencephalon
Vasoconstriction
Thalamus
Computer Simulation
Hypothalamus
Genes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Neurology
  • Behavioral Neuroscience

Cite this

Evaluation of heritable determinants of blood and brain serotonin homeostasis using recombinant inbred mice. / Ye, R.; Carneiro, A. M.D.; Airey, D.; Sanders-Bush, E.; Williams, Robert; Lu, Lu; Wang, J.; Zhang, B.; Blakely, R. D.

In: Genes, Brain and Behavior, Vol. 13, No. 3, 01.03.2014, p. 247-260.

Research output: Contribution to journalArticle

Ye, R. ; Carneiro, A. M.D. ; Airey, D. ; Sanders-Bush, E. ; Williams, Robert ; Lu, Lu ; Wang, J. ; Zhang, B. ; Blakely, R. D. / Evaluation of heritable determinants of blood and brain serotonin homeostasis using recombinant inbred mice. In: Genes, Brain and Behavior. 2014 ; Vol. 13, No. 3. pp. 247-260.
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