Mapping a locus for alcohol physical dependence and associated withdrawal to a 1.1 Mb interval of mouse chromosome 1 syntenic with human chromosome 1q23.2-23.3

L. Kozell, John Belknap, J. R. Hofstetter, A. Mayeda, Kari Buck

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Physiological dependence and associated withdrawal episodes are thought to constitute a motivational force perpetuating continued alcohol use/abuse. Although no animal model duplicates alcoholism, models for specific factors, like the withdrawal syndrome, are useful to identify potential determinants of liability in humans. We previously detected quantitative trait loci (QTLs) with large effects on predisposition to physical dependence and associated withdrawal following chronic or acute alcohol exposure to a large region of chromosome 1 in mice (Alcdp1 and Alcw1, respectively). Here, we provide the first confirmation of Alcw1 in a congenic strain, and, using interval-specific congenic strains, narrow its position to a minimal 1.1 Mb (maximal 1.7 Mb) interval syntenic with human chromosome 1q23.2-23.3. We also report the development of a small donor segment congenic that confirms capture of a gene(s) affecting physical dependence after chronic alcohol exposure within this small interval. This congenic will be invaluable for determining whether this interval harbors a gene(s) involved in additional alcohol responses for which QTLs have been detected on distal chromosome 1, including alcohol consumption, alcohol-conditioned aversion and -induced ataxia. The possibility that this QTL plays an important role in such diverse responses to alcohol makes it an important target. Moreover, human studies have identified markers on chromosome 1q associated with alcoholism, although this association is still suggestive and mapped to a large region. Thus, the fine mapping of this QTL and analyses of the genes within the QTL interval can inform developing models for genetic determinants of alcohol dependence in humans.

Original languageEnglish (US)
Pages (from-to)560-567
Number of pages8
JournalGenes, Brain and Behavior
Volume7
Issue number5
DOIs
StatePublished - Jul 2008

Fingerprint

Chromosomes, Human, Pair 1
Quantitative Trait Loci
Human Chromosomes
Alcoholism
Alcohols
Genetic Models
Ataxia
Genetic Markers
Alcohol Drinking
Genes
Animal Models

Keywords

  • C57BL/6J (B6)
  • Convulsion
  • DBA/2J (D2)
  • Ethanol
  • Interval-specific congenic strain
  • Quantitative trait locus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Genetics

Cite this

Mapping a locus for alcohol physical dependence and associated withdrawal to a 1.1 Mb interval of mouse chromosome 1 syntenic with human chromosome 1q23.2-23.3. / Kozell, L.; Belknap, John; Hofstetter, J. R.; Mayeda, A.; Buck, Kari.

In: Genes, Brain and Behavior, Vol. 7, No. 5, 07.2008, p. 560-567.

Research output: Contribution to journalArticle

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