Behavior Genetics

, Volume 39, Issue 2, pp 183–191 | Cite as

Studies on Syntaxin 12 and Alcohol Preference Involving C57BL/6J and DBA/2J Strains of Mice

ORIGINAL RESEARCH

Abstract

C57BL/6J and DBA/2J inbred mouse strains have been extensively studied for the genetic dissection of alcohol-related phenotypes. We have previously found Syntaxin 12 to be associated with alcohol preference in C57BL/6J and DBA/2J due to its strain-specific and ethanol responsive expression in the male brain. In the current study, we combined genetic and expression analyses to assess the segregation of Syntaxin 12 c.*1370G>A polymorphism with its strain-specific expression and alcohol preference in an F2 population (N = 427) derived from C57BL/6J and DBA/2J strains. Syntaxin 12 c.*1370G>A polymorphism was found to segregate with alcohol preference in the B6D2F2 population and a correlation was identified between Syntaxin 12 expression and alcohol preference in the selected B6D2F2 males (= −0.473, r2 = 0.22). We followed up our analysis in the BXD RI lines using resources from WebQTL and the Mouse Phenome Database. Our study detected significant associations of Syntaxin 12 molecular variants with its level of expression and alcohol preference in B6D2F2 males. Overall, our findings support a role for Syntaxin 12 as a potential contributor to alcohol preference in mice.

Keywords

Syntaxin 12 Alcohol preference C57BL/6J DBA/2J Candidate gene 

Supplementary material

10519_2008_9249_MOESM1_ESM.doc (11 kb)
(DOC 10 kb)

References

  1. Bachmanov AA, Tordoff MG, Beauchamp GK (1996) Ethanol consumption and taste preferences in C57BL/6ByJ and 129/J mice. Alcohol Clin Exp Res 20(2):201–206. doi:10.1111/j.1530-0277.1996.tb01630.x
  2. Belknap JK, Atkins AL (2001) The replicability of QTLs for murine alcohol preference drinking behavior across eight independent studies. Mamm Genome 12(12):893–899. doi:10.1007/s00335-001-2074-2 PubMedCrossRefGoogle Scholar
  3. Belknap JK, Crabbe JC, Young ER (1993) Voluntary consumption of ethanol in 15 inbred mouse strains. Psychopharmacology 112(4):503–510. doi:10.1007/BF02244901 PubMedCrossRefGoogle Scholar
  4. Fernandez JR, Vogler GP, Tarantino LM, Vignetti S, Plomin R, McClearn GE (1999) Sex-exclusive quantitative trait loci influences in alcohol-related phenotypes. Am J Med Genet 88(6):647–652. doi:10.1002/(SICI)1096-8628(19991215)88:6<647::AID-AJMG13>3.0.CO;2-6PubMedCrossRefGoogle Scholar
  5. Ford MM, Eldridge JC, Samson HH (2002) Microanalysis of ethanol self-administration: estrous cycle phase-related changes in consumption patterns. Alcohol Clin Exp Res 26(5):635–643. doi:10.1111/j.1530-0277.2002.tb02585.x PubMedCrossRefGoogle Scholar
  6. Lee SH, Valtschanoff JG, Kharazia VN, Weinberg R, Sheng M (2001) Biochemical and morphological characterization of an intracellular membrane compartment containing AMPA receptors. Neuropharmacology 41(6):680–692. doi:10.1016/S0028-3908(01)00124-1 PubMedCrossRefGoogle Scholar
  7. Lewohl JM, Wang L, Miles MF, Zhang L, Dodd PR, Harris RA (2000) Gene expression in human alcoholism: microarray analysis of frontal cortex. Alcohol Clin Exp Res 24(12):1873–1882. doi:10.1111/j.1530-0277.2000.tb01993.x PubMedCrossRefGoogle Scholar
  8. Mayfield RD, Lewohl JM, Dodd PR, Herlihy A, Liu J, Harris RA (2002) Patterns of gene expression are altered in the frontal and motor cortices of human alcoholics. J Neurochem 81(4):802–813. doi:10.1046/j.1471-4159.2002.00860.x PubMedCrossRefGoogle Scholar
  9. McClearn GE, Rodgers DA (1959) Differences in alcohol preference among inbred strains of mice. Q J Stud Alcohol 20:691–695Google Scholar
  10. McClearn GE, Tarantino LM, Rodriguez LA, Jones BC, Blizard DA, Plomin R (1997) Genotypic selection provides experimental confirmation for an alcohol consumption quantitative trait locus in mouse. Mol Psychiatry 2(6):486–489. doi:10.1038/sj.mp.4000320 PubMedCrossRefGoogle Scholar
  11. Moykkynen T, Korpi ER, Lovinger DM (2003) Ethanol inhibits alpha-amino-3-hydyroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor function in central nervous system neurons by stabilizing desensitization. J Pharmacol Exp Ther 306(2):546–555. doi:10.1124/jpet.103.050666 PubMedCrossRefGoogle Scholar
  12. Mulligan MK, Ponomarev I, Hitzemann RJ, Belknap JK, Tabakoff B, Harris RA, Crabbe JC, Blednov YA, Grahame NJ, Phillips TJ et al (2006) Toward understanding the genetics of alcohol drinking through transcriptome meta-analysis. Proc Natl Acad Sci USA 103(16):6368–6373. doi:10.1073/pnas.0510188103 PubMedCrossRefGoogle Scholar
  13. Mulligan MK, Ponomarev I, Boehm SLII, Owen JA, Levin PS, Berman AE, Blednov YA, Crabbe JC, Williams R, Miles M et al (2008) Alcohol trait and transcriptional genomic analysis of C57BL/6 substrains. Genes Brain Behav 7(6):677–689PubMedCrossRefGoogle Scholar
  14. Murphy BC, Chiu T, Harrison M, Uddin RK, Singh SM (2002) Examination of ethanol responsive liver and brain specific gene expression, in the mouse strains with variable ethanol preferences, using cDNA expression arrays. Biochem Genet 40(11–12):395–410. doi:10.1023/A:1020777528602 PubMedCrossRefGoogle Scholar
  15. Nutt D (1999) Alcohol and the brain pharmacological insights for psychiatrists. Br J Psychiatry 175:114–119. doi:10.1192/bjp.175.2.114 PubMedCrossRefGoogle Scholar
  16. Park M, Penick EC, Edwards JG, Kauer JA, Ehlers MD (2004) Recycling endosomes supply AMPA receptors for LTP. Science 305(5692):1972–1975. doi:10.1126/science.1102026 PubMedCrossRefGoogle Scholar
  17. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9):e45. doi:10.1093/nar/29.9.e45
  18. Phillips TJ, Crabbe JC, Metten P, Belknap JK (1994) Localization of genes affecting alcohol drinking in mice. Alcohol Clin Exp Res 18(4):931–941. doi:10.1111/j.1530-0277.1994.tb00062.x PubMedCrossRefGoogle Scholar
  19. Rimondini R, Arlinde C, Sommer W, Heilig M (2002) Long-lasting increase in voluntary ethanol consumption and transcriptional regulation in the rat brain after intermittent exposure to alcohol. FASEB J 16(1):27–35. doi:10.1096/fj.01-0593com PubMedCrossRefGoogle Scholar
  20. Singh SM, Treadwell J, Kleiber ML, Harrison M, Uddin RK (2007) Analysis of behavior using genetical genomics in mice as a model: from alcohol preferences to gene expression differences. Genome 50(10):877–897. doi:10.1139/G06-118 PubMedCrossRefGoogle Scholar
  21. Schuckit MA (1994) Low level of response to alcohol as a predictor of future alcoholism. Am J Psychiatry 151(2):184–189PubMedGoogle Scholar
  22. Sokolov BP, Jiang L, Trivedi NS, Aston C (2003) Transcription profiling reveals mitochondrial, ubiquitin and signaling systems abnormalities in postmortem brains from subjects with a history of alcohol abuse or dependence. J Neurosci Res 72(6):756–767. doi:10.1002/jnr.10631 PubMedCrossRefGoogle Scholar
  23. Tarantino LM, McClearn GE, Rodriguez LA, Plomin R (1998) Confirmation of quantitative trait loci for alcohol preference in mice. Alcohol Clin Exp Res 22(5):1099–1105PubMedGoogle Scholar
  24. Teng FY, Wang Y, Tang BL (2001) The syntaxins. Genome Biol 2(11):Reviews3012.1–7Google Scholar
  25. Thibault C, Lai C, Wilke N, Duong B, Olive MF, Rahman S, Dong H, Hodge CW, Lockhart DJ, Miles MF (2000) Expression profiling of neural cells reveals specific patterns of ethanol-responsive gene expression. Mol Pharmacol 58(6):1593–1600PubMedGoogle Scholar
  26. Treadwell JA, Singh SM (2004) Microarray analysis of mouse brain gene expression following acute ethanol treatment. Neurochem Res 29(2):357–369. doi:10.1023/B:NERE.0000013738.06437.a6 PubMedCrossRefGoogle Scholar
  27. Treadwell JA, Pagniello KB, Singh SM (2004) Genetic segregation of brain gene expression identifies retinaldehyde binding protein 1 and syntaxin 12 as potential contributors to ethanol preference in mice. Behav Genet 34(4):425–439. doi:10.1023/B:BEGE.0000023648.78190.ee PubMedCrossRefGoogle Scholar
  28. Wang J, Williams RW, Manly KF (2003) WebQTL: web-based complex trait analysis. Neuroinformatics 1(4):299–308. doi:10.1385/NI:1:4:299 PubMedCrossRefGoogle Scholar
  29. Xu Y, Ehringer M, Yang F, Sikela JM (2001) Comparison of global brain gene expression profiles between inbred long-sleep and inbred short-sleep mice by high-density gene array hybridization. Alcohol Clin Exp Res 25(6):810–818. doi:10.1111/j.1530-0277.2001.tb02284.x PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Department of BiologyUniversity of Western OntarioLondonCanada

Personalised recommendations