The syntaxin binding protein 1 gene (Stxbp1) is a candidate for an ethanol preference drinking locus on mouse chromosome 2.
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 x 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.
Fehr
Christoph
C
Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, and US Department of Veterans Affairs Medical Center, Portland, Oregon 97239, USA.
Shirley
Renee L
RL
Crabbe
John C
JC
Belknap
John K
JK
Buck
Kari J
KJ
Phillips
Tamara J
TJ
D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002875:Chromosomes / Q000235:genetics*; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D005838:Genotype; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D013649:Taste / Q000187:drug effects; D033921:Vesicular Transport Proteins / Q000235:genetics*
D002492:Central Nervous System Depressants; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; D000431:Ethanol