Neurochemical Research

, Volume 32, Issue 7, pp 1099–1112 | Cite as

Mapping of QTLs for Oral Alcohol Self-Administration in B6.C and B6.I Quasi-Congenic RQI Strains

  • Csaba Vadasz
  • Mariko Saito
  • Beatrix M. Gyetvai
  • Melinda Oros
  • Istvan Szakall
  • Krisztina M. Kovacs
  • Vidudala V. T. S. Prasad
  • Grant Morahan
  • Reka Toth
Original paper

Abstract

One strategy to identify neurochemical pathways of addiction is to map the relevant genes. In the present study we used 43 B6.C and 35 B6.I inbred RQI mouse strains, carrying <3% donor genome on C57BL/6ByJ background, for gene mapping. The strains were phenotyped for consumption of alcohol (12% v/v) in a two-bottle-choice paradigm, and genotyped for 396 microsatellite markers. The current mapping study extends our earlier experiment scanning five mouse chromosomes (Vadasz et al. (2000) Scanning of five chromosomes for alcohol consumption loci. Alcohol 22:25–34) to a whole-genome study, and discusses the differences and limitations. Data were analyzed with composite interval (CIM) and multiple interval (MIM) QTL mapping methods. CIM of B6.C strains detected significant QTLs on chrs. 6 and 12. A suggestive, but not significant, locus was detected in the B6.I strains on chr. 12. The best MIM model for B6.C strains confirmed one QTL on chr. 6 and one QTL on chr. 12, while the MIM model for the B6.I strains confirmed the suggestive locus on chr. 12. Some of the QTLs for alcohol consumption are new, while others confirm previously reported QTLs for alcohol preference, and alcohol acceptance.

Keywords

QTL mapping Quasi-congenic mouse Recombinant QTL introgression Ethanol consumption Addiction 

Notes

Acknowledgements

Research described in this article was supported by NIH NIAAA grant AA11031. We thank Rui Fen Mao, Janos Piturca, and Ray Wang for excellent assistance in animal care.

References

  1. 1.
    Mcclearn GE, Rodgers DA (1959) Differences in alcohol preference among inbred strains of mice. Q J Stud Alcohol 20:659–691Google Scholar
  2. 2.
    Belknap JK, Atkins AL (2001) The replicability of QTLs for murine alcohol preference drinking behavior across eight independent studies. Mamm Genome 12:893–899PubMedCrossRefGoogle Scholar
  3. 3.
    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 34:425–439PubMedCrossRefGoogle Scholar
  4. 4.
    Treadwell JA (2006) Integrative strategies to identify candidate genes in rodent models of human alcoholism. Genome 49:1–7PubMedCrossRefGoogle Scholar
  5. 5.
    Fehr C, Shirley RL, Crabbe JC, Belknap JK, Buck KJ, Phillips TJ (2005) The syntaxin binding protein 1 gene (Stxbp1) is a candidate for an ethanol preference drinking locus on mouse chromosome 2. Alcohol Clin Exp Res 29:708–720PubMedCrossRefGoogle Scholar
  6. 6.
    Gill K, Desaulniers N, Desjardins P, Lake K (1998) Alcohol preference in AXB/BXA recombinant inbred mice: gender differences and gender-specific quantitative trait loci. Mamm Genome 9:929–935PubMedCrossRefGoogle Scholar
  7. 7.
    Gill K, Boyle AE (2005) Genetic analysis of alcohol intake in recombinant inbred and congenic strains derived from A/J and C57BL/6J progenitors. Mamm Genome 16:319–331PubMedCrossRefGoogle Scholar
  8. 8.
    Bachmanov AA, Reed DR, Li X, Li S, Beauchamp GK, Tordoff MG (2002) Voluntary ethanol consumption by mice: genome-wide analysis of quantitative trait loci and their interactions in a C57BL/6ByJ × 129P3/J F2 intercross. Genome Res 12:1257–1268PubMedCrossRefGoogle Scholar
  9. 9.
    Grahame NJ, Li TK, Lumeng L (1999) Selective breeding for high and low alcohol preference in mice [In Process Citation]. Behav Genet 29:47–57PubMedCrossRefGoogle Scholar
  10. 10.
    Bice PJ, Foroud T, Carr LG, Zhang L, Liu L, Grahame NJ, Lumeng L, Li TK, Belknap JK (2006) Identification of QTLs influencing alcohol preference in the high alcohol preferring (HAP) and low alcohol preferring (LAP) mouse lines. Behav Genet 36:248–260PubMedCrossRefGoogle Scholar
  11. 11.
    Mcclearn GE, Wilson JR, Meredith W (1970) The use of isogenic and heterogenic mouse stocks in behavioral research. In: Lindzey G., Thiesse DD (eds) Contributions to behavior genetic analysis: the mouse as a prototype. Appleton-Century-Crofts, New York, pp 3–22Google Scholar
  12. 12.
    Vadasz C, Saito M, Gyetvai B, Mikics E, Vadasz C 2nd (2000) Scanning of five chromosomes for alcohol consumption loci. Alcohol 22:25–34PubMedCrossRefGoogle Scholar
  13. 13.
    Vadasz C, Fleischer A, Lafrancois J, Mao RF (1996) Self-administration of ethanol: towards the location of predisposing polygenes in quasi-congenic animal models. Alcohol 13:617–620PubMedCrossRefGoogle Scholar
  14. 14.
    Vadasz C, Saito M, Balla A, Kiraly I, Vadasz C 2nd, Gyetvai B, Mikics E, Pierson D, Brown D, Nelson JC (2000) Mapping of quantitative trait loci for ethanol preference in quasi-congenic strains. Alcohol 20:161–171PubMedCrossRefGoogle Scholar
  15. 15.
    Vadasz C (1990) Development of congenic recombinant inbred neurological animal model lines. Mouse Genome 88:16–18Google Scholar
  16. 16.
    Vadasz C, Sziraki I, Murthy LR, Sasvari-Szekely M, Kabai P, Laszlovszky I, Fleischer A, Juhasz B, Zahorchak R (1994) Transfer of brain dopamine system-specific quantitative trait loci onto a C57BL/6ByJ background. Mamm Genome 5:735–737PubMedCrossRefGoogle Scholar
  17. 17.
    Vadasz C, Sziraki I, Sasvari M, Kabai P, Laszlovszky I, Juhasz B, Zahorchak R (1996) Genomic characterization of two introgression strains (B6.Cb4i5) for the analysis of QTLs. Mamm Genome 7:545–548PubMedCrossRefGoogle Scholar
  18. 18.
    Abiola O, Angel JM, Avner P, Bachmanov AA, Belknap JK, Bennett B, Blankenhorn EP, Blizard DA, Bolivar V, Brockmann GA, Buck KJ, Bureau JF, Casley WL, Chesler EJ, Cheverud JM, Churchill GA, Cook M, Crabbe JC, Crusio WE, Darvasi A, Haan G De, Dermant P, Doerge RW, Elliot RW, Farber CR, Flaherty L, Flint J, Gershenfeld H, Gibson JP, Gu J, Gu W, Himmelbauer H, Hitzemann R, Hsu HC, Hunter K, Iraqi FF, Jansen RC, Johnson TE, Jones BC, Kempermann G, Lammert F, Lu L, Manly KF, Matthews DB, Medrano JF, Mehrabian M, Mittlemann G, Mock BA, Mogil JS, Montagutelli X, Morahan G, Mountz JD, Nagase H, Nowakowski RS, O’hara BF, Osadchuk AV, Paigen B, Palmer AA, Peirce JL, Pomp D, Rosemann M, Rosen GD, Schalkwyk LC, Seltzer Z, Settle S, Shimomura K, Shou S, Sikela JM, Siracusa LD, Spearow JL, Teuscher C, Threadgill DW, Toth LA, Toye AA, Vadasz C, Zant G Van, Wakeland E, Williams RW, Zhang HG, Zou F (2003) The nature and identification of quantitative trait loci: a community’s view. Nat Rev Genet 4:911–916PubMedGoogle Scholar
  19. 19.
    Vadasz C, Sziraki I, Sasvari M, Kabai P, Murthy LR, Saito M, Laszlovszky I (1998) Analysis of the mesotelencephalic dopamine system by quantitative-trait locus introgression. Neurochem Res 23:1337–1354PubMedCrossRefGoogle Scholar
  20. 20.
    Kovacs KM, Szakall I, O’brien D, Wang R, Vinod KY, Saito M, Simonin F, Kieffer BL, Vadasz C (2005) Decreased oral self-administration of alcohol in kappa-opioid receptor knock-out mice. Alcohol Clin Exp Res 29:730–738PubMedCrossRefGoogle Scholar
  21. 21.
    Saito M, Ehringer MA, Toth R, Oros M, Szakall I, Sikela JM, Vadasz C (2003) Variants of kappa-opioid receptor gene and mRNA in alcohol-preferring and alcohol-avoiding mice. Alcohol 29:39–49PubMedCrossRefGoogle Scholar
  22. 22.
    Zeng ZB (1993) Theoretical basis for separation of multiple linked gene effects in mapping quantitative trait loci. Proc Natl Acad Sci USA 90:10972–10976PubMedCrossRefGoogle Scholar
  23. 23.
    Vadasz C, Sziraki I, Murthy LR, Vadasz I, Badalamenti AF, Kobor G, Lajtha A (1987) Genetic determination of mesencephalic tyrosine hydroxylase activity in the mouse. J Neurogenet 4:241–252PubMedGoogle Scholar
  24. 24.
    Bailey DW (1971) Recombinant-inbred strains. An aid to finding identity, linkage, and function of histocompatibility and other genes. Transplantation 11:325–327PubMedCrossRefGoogle Scholar
  25. 25.
    Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucl Acids Res 16:1215PubMedCrossRefGoogle Scholar
  26. 26.
    Jansen RC (1993) Interval mapping of multiple quantitative trait loci. Genetics 135:205–211PubMedGoogle Scholar
  27. 27.
    Zeng ZB (1994) Precision mapping of quantitative trait loci. Genetics 136:1457–1468PubMedGoogle Scholar
  28. 28.
    Wang S, Basten CJ, Zeng ZB (2005) Windows QTL Cartographer 2.5. Department of Statistics, North Carolina State University, Raleigh, NCGoogle Scholar
  29. 29.
    Churchill GA, Doerge RW (1994) Empirical threshold values for quantitative trait mapping. Genetics 138:963–971PubMedGoogle Scholar
  30. 30.
    Kao CH, Zeng ZB, Teasdale RD (1999) Multiple interval mapping for quantitative trait loci. Genetics 152:1203–1216PubMedGoogle Scholar
  31. 31.
    Kao CH, Zeng ZB (1997) General formulas for obtaining the MLEs and the asymptotic variance–covariance matrix in mapping quantitative trait loci when using the EM algorithm. Biometrics 53:653–665PubMedCrossRefGoogle Scholar
  32. 32.
    Toyoda T, Wada A (2004) Omic space: coordinate-based integration and analysis of genomic phenomic interactions. Bioinformatics 20:1759–1765PubMedCrossRefGoogle Scholar
  33. 33.
    Belknap JK, Crabbe JC, Young ER (1993) Voluntary consumption of ethanol in 15 inbred mouse strains. Psychopharmacology 112:503–510PubMedCrossRefGoogle Scholar
  34. 34.
    Downing C, Rodd-Henricks KK, Flaherty L, Dudek BC (2003) Genetic analysis of the psychomotor stimulant effect of ethanol. Genes Brain Behav 2:140–151PubMedCrossRefGoogle Scholar
  35. 35.
    Le Roy I, Pager J, Roubertoux PL (1999) Genetic dissection of gustatory sensitivity to bitterness (sucrose octaacetate) in mice. C R Acad Sci III 322:831–836PubMedGoogle Scholar
  36. 36.
    Risinger FO, Cunningham CL (1998) Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice. Alcohol Clin Exp Res 22:1234–1244PubMedGoogle Scholar
  37. 37.
    Kugaya A, Sanacora G (2005) Beyond monoamines: glutamatergic function in mood disorders. CNS Spectr 10:808–819PubMedGoogle Scholar
  38. 38.
    Lush IE (1984) The genetics of tasting in mice. III. Quinine. Genet Res 44: 151–160PubMedCrossRefGoogle Scholar
  39. 39.
    Singer JB, Hill AE, Nadeau JH, Lander ES (2005) Mapping quantitative trait loci for anxiety in chromosome substitution strains of mice. Genetics 169:855–862PubMedCrossRefGoogle Scholar
  40. 40.
    Primo-Parmo SL, Sorenson RC, Teiber J, La Du BN (1996) The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family. Genomics 33:498–507PubMedCrossRefGoogle Scholar
  41. 41.
    Nelson TM, Munger SD, Boughter JD Jr (2005) Haplotypes at the Tas2r locus on distal chromosome 6 vary with quinine taste sensitivity in inbred mice. BMC Genet 6:32PubMedCrossRefGoogle Scholar
  42. 42.
    Harder DB, Whitney G (1998) A common polygenic basis for quinine and PROP avoidance in mice. Chem Senses 23:327–332PubMedCrossRefGoogle Scholar
  43. 43.
    Palmer AA, Verbitsky M, Suresh R, Kamens HM, Reed CL, Li N, Burkhart-Kasch S, Mckinnon CS, Belknap JK, Gilliam TC, Phillips TJ (2005) Gene expression differences in mice divergently selected for methamphetamine sensitivity. Mamm Genome 16:291–305PubMedCrossRefGoogle Scholar
  44. 44.
    Kelly MA, Low MJ, Phillips TJ, Wakeland EK, Yanagisawa M (2003) The mapping of quantitative trait loci underlying strain differences in locomotor activity between 129S6 and C57BL/6J mice. Mamm Genome 14:692–702PubMedCrossRefGoogle Scholar
  45. 45.
    Boyle AE, Gill K (2001) Sensitivity of AXB/BXA recombinant inbred lines of mice to the locomotor activating effects of cocaine: a quantitative trait loci analysis. Pharmacogenetics 11:255–264PubMedCrossRefGoogle Scholar
  46. 46.
    Jones BC, Tarantino LM, Rodriguez LA, Reed CL, Mcclearn GE, Plomin R, Erwin VG (1999) Quantitative-trait loci analysis of cocaine-related behaviours and neurochemistry. Pharmacogenetics 9:607–617PubMedCrossRefGoogle Scholar
  47. 47.
    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 88:647–652PubMedCrossRefGoogle Scholar
  48. 48.
    Bachmanov AA, Kiefer SW, Molina JC, Tordoff MG, Duffy VB, Bartoshuk LM, Mennella JA (2003) Chemosensory factors influencing alcohol perception, preferences, and consumption. Alcohol Clin Exp Res 27:220–231PubMedCrossRefGoogle Scholar
  49. 49.
    Tarantino LM, Mcclearn GE, Rodriguez LA, Plomin R (1998) Confirmation of quantitative trait loci for alcohol preference in mice. Alcohol Clin Exp Res 22:1099–1105PubMedGoogle Scholar
  50. 50.
    Copeland NG, Jenkins NA, Gilbert DJ, Eppig JT, Maltais LJ, Miller JC, Dietrich WF, Weaver A, Lincoln SE, Steen RG et al (1993) A genetic linkage map of the mouse: current applications and future prospects. Science 262:57–66Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Csaba Vadasz
    • 1
    • 2
  • Mariko Saito
    • 1
    • 2
  • Beatrix M. Gyetvai
    • 1
  • Melinda Oros
    • 1
  • Istvan Szakall
    • 1
  • Krisztina M. Kovacs
    • 1
  • Vidudala V. T. S. Prasad
    • 1
  • Grant Morahan
    • 3
  • Reka Toth
    • 1
  1. 1.Laboratory of Neurobehavioral GeneticsNathan S. Kline Institute for Psychiatric ResearchOrangeburgUSA
  2. 2.Department of PsychiatryNew York University Medical CenterNew YorkUSA
  3. 3.Diabetes Research CentreWestern Australian Institute for Medical ResearchPerthAustralia

Personalised recommendations