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Derivation and Characterization of Replicate High- and Low-Alcohol Preferring Lines of Mice and a High-Drinking Crossed HAP Line

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Abstract

Selectively breeding lines of mice and rats to differ in alcohol intake has proven useful for defining which traits correlate with high alcohol drinking behavior, as well as for creating animal models of alcoholism. This study reports the derivation of two novel sets of selected lines, High Alcohol Preferring (HAP) and Low Alcohol Preferring (LAP) replicate 2 and 3 lines. Mice were mass-selected using the same procedure as in the replicate 1 lines: using HS/Ibg as a progenitor, mice were selected for differences in 2-bottle choice intake of 10% alcohol during a 4-week testing period. In addition, another high-drinking line, the crossed HAP (cHAP) line was selectively bred from a progenitors that were a cross of replicate 1 (S27) × replicate 2 (S21) HAP lines. All lines were characterized for saccharin intake. Overall, the response to selection of the HAP and LAP replicate 2 and 3 lines was quite similar. As anticipated, following selection, the cHAP line drank more than either parent HAP line (consuming 26.0 g/kg per day of alcohol by S11), suggesting that this method of crossing replicate lines and selecting from that cross captures more alleles than any single selected line, as well as producing a line with exceptionally high voluntary alcohol intake. As expected, saccharin consumption was highly associated with alcohol consumption; data from 7 lines (HAP 1, 2, and 3, LAP 1, 2, and 3, and cHAP) indicated a genetic correlation between 10% alcohol and 0.32% saccharin intake of 0.91. Overall, these findings show the practicality of developing replicate lines divergent in alcohol preference, and validate a novel procedure for generating very high-drinking mouse populations.

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Acknowledgments

This work was supported by the Indiana Alcohol Research Center (P60 07611) to David Crabb, U01 AA13483 to NJG, and F31 AA016430 to BGO. Thanks are also extended to Lawrence Lumeng, who initiated selection of replicate 1 HAP and LAP mice.

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Authors and Affiliations

  1. Department of Psychology, Indiana University Purdue University at Indianapolis, 402 N. Blackford St. LD120F, Indianapolis, IN, 46202, USA

    Brandon Oberlin, Christina Best, Liana Matson, Angela Henderson & Nicholas Grahame

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  1. Brandon Oberlin
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  2. Christina Best
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  3. Liana Matson
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  4. Angela Henderson
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  5. Nicholas Grahame
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Correspondence to Nicholas Grahame.

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Edited by Tamara Phillips.

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Oberlin, B., Best, C., Matson, L. et al. Derivation and Characterization of Replicate High- and Low-Alcohol Preferring Lines of Mice and a High-Drinking Crossed HAP Line. Behav Genet 41, 288–302 (2011). https://doi.org/10.1007/s10519-010-9394-5

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  • DOI: https://doi.org/10.1007/s10519-010-9394-5

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