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Identification of QTLs Influencing Alcohol Preference in the High Alcohol Preferring (HAP) and Low Alcohol Preferring (LAP) Mouse Lines

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The High- and Low-Alcohol Preferring (HAP1/LAP1 and HAP2/LAP2) mouse lines were developed by selective breeding for differences in alcohol preference. They represent the only extant selectively bred mouse lines developed for this alcohol phenotype. Therefore, they provide a unique resource for QTL detection and mapping. Importantly, neither of the replicate lines is inbred and therefore, novel study designs can be employed to detect loci contributing to alcohol preference. Two independent studies, with very different approaches, were conducted in the HAP and LAP replicate lines. In Study 1, microsatellite markers were genotyped in the replicate HAP1/LAP1 and HAP2/LAP2 mice in QTL regions nominated by other mouse RI and F2 studies in order to detect divergence of allele frequencies in the two oppositely selected lines. Significant differences in allele frequencies were observed in the HAP1/LAP1 mice with markers on chromosome 9 (p<0.01). In the HAP2/LAP2 mice, significant differences in allele frequencies were identified on chromosomes 2 and 9 (p<0.01). In Study 2, a genome-wide screen was performed in a sample of 432 HAP1×LAP1 F2 animals and a QTL on chromosome 9 (LOD=5.04) was found which met criteria for genome wide significance (p<0.001). Gender specific analyses supported a greater effect of the QTL among female mice (LOD=5.19; p<0.0008) than male mice (LOD=1.19). This study provides additional evidence and confirmation that specific regions on chromosomes 9 and perhaps 2 are important for alcohol preference.

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Acknowledgments

We would like to thank Dr. Howard Edenberg for allowing us to use the Core Facility to perform the genotyping. We especially thank Dr. Tian Huijun for her assistance in using the Genetic Analyzer. A special thanks goes to Christina Payne for her work in the development and phenotyping of the F2 mice used in the genome screen. We also thank Dr. Michael Econs and members of his laboratory for their assistance and advice. This project was supported by NIH/NIAAA Grants KO1 AA000296 and K02 AA00285.

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Authors and Affiliations

  1. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Paula J. Bice, Lucinda G. Carr, Lili Zhang & Lawrence Lumeng

  2. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Tatiana Foroud & Lixiang Liu

  3. Department of Psychology, Indiana University Purdue University at Indianapolis, 402 N Blackford St. LD125, Indianapolis, IN, 46202, USA

    Nicholas J. Grahame

  4. National Institute of Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 2001, Bethesda, MD, 20892, USA

    Ting-Kai Li

  5. VA Medical Center (R&D5), and Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, 97239, USA

    John K. Belknap

  6. Department of Medicine, Indiana University School of Medicine, Room 411, 975 W. Walnut St., Indianapolis, IN, 46202, USA

    Paula J. Bice

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  1. Paula J. Bice
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  2. Tatiana Foroud
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Correspondence to Paula J. Bice.

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Bice, P.J., Foroud, T., Carr, L.G. et al. Identification of QTLs Influencing Alcohol Preference in the High Alcohol Preferring (HAP) and Low Alcohol Preferring (LAP) Mouse Lines. Behav Genet 36, 248–260 (2006). https://doi.org/10.1007/s10519-005-9019-6

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