Skip to main content
SpringerLink
Log in

Genetic analysis of alcohol intake in recombinant inbred and congenic strains derived from A/J and C57BL/6J progenitors

  • Published:
Mammalian Genome Aims and scope Submit manuscript

Abstract

The objective of the present study was to map quantitative trait loci (QTL) for alcohol intake using A × B/B × A recombinant inbred (RI) and AcB/BcA recombinant congenic (RC) strains of mice that were independently derived from the A/J and C57BL/6J progenitors. Mice were screened for levels of alcohol consumption with four days of forced exposure to alcohol, followed by three weeks of free choice between water and a 10% alcohol solution. Alcohol consumption data previously collected for 27 A × B/B × A RI strains were reanalyzed using a larger marker set and composite interval mapping. The reanalysis found markers on Chromosome 2 (D2Mit74, 107 cM) (males and females) and on Chromosome 11 (Pmv22, 8 cM) (females only) that exceeded the threshold for significant loci, and found suggestive loci (in males) on Chromosomes 10 (D10 Mit126, 21 cM), 12 (D12Mit37, 1 cM), 15 (Pdgfb, 46.8 cM), and 16 (D16Mit125, 29 cM). An additional suggestive locus was identified in female RI mice on Chromosome 11 (D11Mit120, 47.5 cM). Composite interval mapping (CIM) analysis indicated that there was a significant association between loci at Pdgfb and D2Mit74 in both males and females. Analysis of the AcB/BcA RC strains identified 11 QTL on Chromosomes 2, 3, 5,6, 7, 8, 9, 10, 12, 13, and 15. QTL on Chromosomes 7, 10, 12, and 15 were identified in both the A × B/B × A RI and AcB/BcA RC strains of mice. Additional QTLs identified on Chromosomes 2, 3, 7, 11, and 15 overlap with those previously identified in the literature using strains of mice with a C57BL/6J progenitor.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

VAC:

voluntary alcohol consumption

RI:

recombinant inbred

RC:

recombinant congenic

QTL:

quantitative trait locus

LRS:

likelihood ratio statistic

CIM:

composite interval mapping

References

  • Avital A, Richter–Levin G, Leschiner S, Spanier I, Veenman L, et al. (2001) Acute and repeated swim stress effects on peripheral benzodiazepine receptors in the rat hippocampus, adrenal, and kidney. Neuropsychopharmacology 25(5), 669–678

    Article  PubMed  Google Scholar 

  • Belknap JK, Atkins AL (2001) The replicability of QTLs for murine alcohol preference drinking behaviour across eight independent studies. Mamm Genome 12, 893–899

    Article  PubMed  Google Scholar 

  • Belknap JK, Mitchell SR, O’Toole LA, Helms ML, Crabbe JC (1996) Type 1 and type 11 error rates for quantitative trait loci (QTL) mapping studies using recombinant inbred mouse strains. Behav Genet 26, 149–160

    PubMed  Google Scholar 

  • Belknap JK, Richards SP, O’Toole LA, Helms ML, Phillips TJ (1997) Short-term selective breeding as a tool for QTL mapping: ethanol preference drinking in mice. Behav Genet 27, 55–66

    Article  PubMed  Google Scholar 

  • Cardoso RA, Brozowski SJ, Chavez-Noriega LE, Harpold M, Valenzvela CF, et al. (1999) Effects of ethanol on recombinant human neuronal nicotinic acetylcholine receptors expressed in xenopus oocytes. J Pharmacol Exp Ther 289(2), 774–780

    Google Scholar 

  • Churchill GA, Doerge RW (1994) Empirical threshold values for quantitative trait mapping. Genetics 138, 963–971

    PubMed  Google Scholar 

  • Gehle VM, Erwin VG (1998) Common quantitative trait loci for alcohol-related behaviours and CNS neurotensin measures: voluntary ethanol consumption. Alcohol Clin Exp Res 22, 401–408

    PubMed  Google Scholar 

  • Gill K, Desaulniers N, Desjardins P, Lake K (1998) Alcohol preference in A × B/B × A recombinant inbred mice: Gender differences and gender-specific quantitative trait loci. Mamm Genome 9, 929–935

    Article  PubMed  Google Scholar 

  • Gorbounova O, Svensson AL, Jonsson P, Mousavi M, Miao H, et al. (1998) Chronic ethanol treatment decreases [3H] epibatidine and [3H] nicotine binding and differentially regulates mRNA levels of nicotinic acetylcholine receptor subunits expressed in MIO and SH-SY5Y neuroblastoma cells. J Neurochem 70(3), 1134–1142

    PubMed  Google Scholar 

  • Fortin A, Diez E, Rochefort D, Laroche L, Malo D, et al. (2001) Recombinant congenic strains derived from A/J and C57BL/6J: a tool for genetic dissection of complex traits. Genomics 74(1), 21–35

    Article  Google Scholar 

  • Groot PC, Moen C, Dietrich W, Stoye JP, Lander ES, et al. (1992) The recombinant congenic strains for analysis of multigenic traits: genetic composition. FASEB J 6, 2826–2835

    PubMed  Google Scholar 

  • Jansen RC (1994) Controlling the type I and type II errors in mapping quantitative trait loci. Genetics 138(3), 871–881

    PubMed  Google Scholar 

  • Lander ES, Kruglyak L (1995) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 1, 241–247

    Article  Google Scholar 

  • Manly KF (2001) Users manual for Map Manager classic and Map Manager QTX (url: http://mcbio.med.buffalo.edu/MMM/MMM.html

  • Manly KF, Olsen JM (1999) Overview of QTL mapping software and introduction to Map Manager QT. Mamm Genome 10, 327–334

    Article  PubMed  Google Scholar 

  • Melo JA, Shendure J, Pociask K, Silver LM (1996) Identification of sex-specific quantitative trait loci controlling ethanol preference in C57BL/6 mice. Nat Genet 13, 147–153

    Article  PubMed  Google Scholar 

  • Morato GS, Ferreira VM, Ferrara P, Farges RC (2001) Effects of central and systemic injections of peripheral benzodiazepine receptor ligands on the anxiolytic actions of ethanol in rats. Addict Biol 6(2), 129–136

    Article  PubMed  Google Scholar 

  • Mouse Genome Database (MGD) (2002) Mouse Genome Informatics, The Jackson Laboratory, Bar Harbor, ME. Available at: http://www.informatics. jax.org/

  • Nesbitt MN, Skamene E (1984) Recombinant inbred mouse strains derived from A/J and C57BL/6J: A tool for the study of genetic mechanisms in host resistance to infection and malignancy. J Leukoc Biol 36, 357–364

    PubMed  Google Scholar 

  • Okuyama S, Chaki S, Yoshikawa R, Ogawa S, Suzuki Y, et al. (1999) Neuropharmacological profile of peripheral benzodiazepine receptor agonists, DAA1097 and DAA1106. Life Sci 64(16), 1455–1464

    Article  PubMed  Google Scholar 

  • Otto SP, Jones CD (2000) Detecting the undetected: estimating the total number of loci underlying a quantitative trait. Genetics 156(4), 2093–2107

    PubMed  Google Scholar 

  • Peirce JL, Derr R, Shendure J, Kolata T, Silver LM (1998) A major influence of sex-specific loci on alcohol preference in C57BL/6 and DBA/2 inbred mice. Mamm Genome 9, 942–948

    Article  PubMed  Google Scholar 

  • Phillips TJ, Crabbe JC, Metten P, Belknap JK (1994) Localization of genes affecting alcohol drinking in mice. Alcohol Clin Exp Res 18, 931–941

    PubMed  Google Scholar 

  • Phillips TJ, Belknap JK, Buck KJ, Cunningham CL (1998) Genes on mouse Chromosomes 2 and 9 determine variation in ethanol consumption. Mamm Genome 9, 936–941

    Article  PubMed  Google Scholar 

  • Plomin R, McClearn GE (1993) Quantitative trait loci (QTL) analyses and alcohol-related behaviors. Behav Genet 23(2), 197–211

    Article  PubMed  Google Scholar 

  • Rodriguez LA, Plomin R, Blizard DA, Jones BC, McClearn GE (1994) Alcohol acceptance, preference, and sensitivity in mice. I. Quantitative genetic analysis using B × D recombinant inbred strains. Alcohol Clin Exp Res 18, 1416–1422

    PubMed  Google Scholar 

  • Rodriguez LA, Plomin R, Blizard DA, Jones BC, McClearn GE (1995) Alcohol acceptance, preference, and sensitivity in mice. II. Quantitative trait loci mapping analysis using B × D recombinant inbred strains. Alcohol Clin Exp Res 19, 367–373

    PubMed  Google Scholar 

  • Syapin PJ, Alkana RL (1988) Chronic ethanol exposure increases peripheral-type benzodiazepine receptors in the brain. Eur J Pharmacol 147(1), 101–109

    Article  PubMed  Google Scholar 

  • Tamborska E, Marangos PJ (1986) Brain benzodiazepine binding sites in ethanol dependent and withdrawal states. Life Sci 38(5), 465–472

    Article  PubMed  Google Scholar 

  • Tarantino LM, McClearn GE, Rodriquez LA, Plomin R (1998) Confirmation of quantitative trait loci for alcohol preference in mice. Alcohol Clin Exp Res 23, 1099–1105

    Google Scholar 

  • Taylor BA, Phillips SJ (1995) Typing recombinant inbred mouse strains for microsatellite markers on Chromosomes 10, 16, 18, 19, and X. Mamm Genome 6(8), 493–498

    Article  PubMed  Google Scholar 

  • Tritto T, Marley RJ, Bastidas D, Stitzel JA, Collins AC (2001) Potential regulation of nicotine and ethanol actions by alpha 4-containing nicotinic receptors. Alcohol 24, 69–78

    Article  PubMed  Google Scholar 

  • Vadasz C, Saito M, Balla A, Kiraly I, Vadasz C II, et al. (2000a) Mapping of quantitative trait loci for ethanol preference in quasi-congenic strains. Alcohol 20, 161–171

    Article  Google Scholar 

  • Vadasz C, Saito M, Gyetvai B, Mikics E, Vadasz C II (2000b) Scanning of five chromosomes for alcohol consumption loci. Alcohol 22, 25–34

    Article  Google Scholar 

  • Whatley VJ, Johnson TE, Erwin VG (1999) Identification and confirmation of quantitative trait loci regulating alcohol consumption in congenic strains of mice. Alcohol Clin Exp Res 23(7), 1262–1271

    PubMed  Google Scholar 

  • Zeng ZB (1994) Precision mapping of quantitative trait loci. Genetics 136(4), 1457–1468

    PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by operating grants awarded to K. Gill by the Canadian Institutes of Health Research (CIHR) and the Alcohol Beverage Medical Research Foundation (ABMRF). The authors acknowledge Emerillon Therapeutics Inc. and Dr. E. Skamene, Director of the Research Institute of the McGill University Health Centre, for providing access to the AcB/BcA RC mice and genetic maps.

Author information

Authors and Affiliations

  1. Research Institute of the McGill University Health Centre and Psychiatry Department, McGill University, Montreal, Quebec, Canada

    Kathryn Gill & Alan E. Boyle

Authors
  1. Kathryn Gill
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alan E. Boyle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kathryn Gill.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gill, K., Boyle, A.E. Genetic analysis of alcohol intake in recombinant inbred and congenic strains derived from A/J and C57BL/6J progenitors. Mamm Genome 16, 319–331 (2005). https://doi.org/10.1007/s00335-004-2239-x

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00335-004-2239-x

Keywords

Search

Navigation