The syntaxin binding protein 1 gene (Stxbp1) is a candidate for an ethanol preference drinking locus on mouse chromosome 2

Christoph Fehr, Renee L. Shirley, John Jr Crabbe, John Belknap, Kari Buck, Tamara Phillips

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Background: We previously mapped a quantitative trait locus (QTL) for ethanol preference drinking to mouse chromosome 2 (mapped with high confidence, LOD = 15.5, p = 3 × 10-16). The specific gene(s) in the QTL interval responsible for phenotypic variation in ethanol preference drinking has not been identified. Methods: In the current study, we investigated the association of the syntaxin binding protein 1 gene (Stxbp1) with ethanol preference drinking and other ethanol traits using a panel of B6 X D2 (BXD) recombinant inbred (RI) strains derived from the C57BL/6J (B6) and DBA/2J (D2) inbred mouse strains. Confirmation analyses for ethanol consumption and withdrawal were performed using a large B6D2 F2 cross, short-term selected lines derived from the B6 and D2 progenitor strains, and standard inbred strains. Results: BXD RI strain analysis detected provisional associations between Stxbp1 molecular variants and ethanol consumption, as well as severity of acute ethanol withdrawal, ethanol-conditioned taste aversion, and ethanol-induced hypothermia. Confirmation analyses using three independent genetic models supported the involvement of Stxbp1 in ethanol preference drinking but not in ethanol withdrawal. Conclusions: Stxbp1 encodes a Sec1/Munc18-type protein essential for vesicular neurotransmitter release. The present study provides supporting evidence for the involvement of Stxbp1 in ethanol preference drinking.

Original languageEnglish (US)
Pages (from-to)708-720
Number of pages13
JournalAlcoholism: Clinical and Experimental Research
Volume29
Issue number5
DOIs
StatePublished - May 2005
Externally publishedYes

Fingerprint

Qa-SNARE Proteins
Chromosomes, Human, Pair 2
Chromosomes
Drinking
Carrier Proteins
Ethanol
Genes
Quantitative Trait Loci
Munc18 Proteins
Hypothermia
Induced Hypothermia
Inbred Strains Mice
Genetic Models
Neurotransmitter Agents

Keywords

  • Dependence and Withdrawal
  • Sec-1/Munc-18
  • Soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor
  • Vesicle Release

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

The syntaxin binding protein 1 gene (Stxbp1) is a candidate for an ethanol preference drinking locus on mouse chromosome 2. / Fehr, Christoph; Shirley, Renee L.; Crabbe, John Jr; Belknap, John; Buck, Kari; Phillips, Tamara.

In: Alcoholism: Clinical and Experimental Research, Vol. 29, No. 5, 05.2005, p. 708-720.

Research output: Contribution to journalArticle

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