Quantitative trait loci for traits related to affective disorder in inbred strains of mice

J. I. Nurnberger, J. Trofatter, A. Mayeda, B. Tarricone, J. Hofstetter, J. Simon, N. Grahame, D. K. Lahiri, J. Belknap, J. Hingtgen

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

We have examined several behavioral and neurochemical traits in the mouse that bear analogies to human affective disorder. Decreased motor activity following restraint stress is a behavioral response seen in C57BL6J (B) mice but not in DBA2J (D). This response is preventable by pretreatment with antidepressant agents. The Quantitative Trait Locus (QTL) method, applied to BXD recombinant inbred (RI) strains, identified loci for changes in activity following restraint on chromosome 11 and chromosome 3. These will be followed up with studies in F2 mice. Choline uptake is the rate-limiting step in acetylcholine synthesis; it is increased in B mice compared to D in several brain regions. Increased cholinergic activity has also been associated with human affective disorder. A QTL for high affinity choline uptake on chromosome 17 was found in BXD RI strains and confirmed in F2s. The LOD score is presently about 9. We are studying candidate genes in this region. Circadian rhythms of motor activity show significantly different periods (tau) in B and D mice. These circadian effects are significantly modified with lithium pretreatment. QTLs for tau are noted on mouse chromosomes 1, 4, 9, 11, and 13. Some of the human areas syntenic to the QTLs identified above are also areas of interest in the NIMH Genetics Initiative Bipolar Dataset.

Original languageEnglish (US)
Number of pages1
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume81
Issue number6
StatePublished - Nov 6 1998

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Nurnberger, J. I., Trofatter, J., Mayeda, A., Tarricone, B., Hofstetter, J., Simon, J., Grahame, N., Lahiri, D. K., Belknap, J., & Hingtgen, J. (1998). Quantitative trait loci for traits related to affective disorder in inbred strains of mice. American Journal of Medical Genetics - Neuropsychiatric Genetics, 81(6).