AA and ANA rats exhibit the R100Q mutation in the GABAA receptor α6 subunit

Carr, Lucinda G.; Spence, John P.; Peter Eriksson, C.J.; Lumeng, Lawrence; Li, Ting-Kai

doi:10.1016/j.alcohol.2003.07.003

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Volume 31, Issue 1 , Pages 93-97, August 2003

AA and ANA rats exhibit the R100Q mutation in the GABA_A receptor α₆ subunit

Lucinda G. Carr
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
- Department of Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
- Corresponding author. Departments of Medicine and Pharmacology, Indiana University School of Medicine, 975 West Walnut Street, IB 407, Indianapolis, IN 46202, USA. Tel.: +1-317-274-0152; fax: +1-317-278-4983.
John P. Spence
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
C.J. Peter Eriksson
- Department of Mental Health and Alcohol Research, National Public Health Institute, 00101 Helsinki, Finland
Lawrence Lumeng
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Ting-Kai Li
- National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA

Received 12 May 2003; received in revised form 20 June 2003; accepted 17 July 2003.

Editor: T.R. Jerrells

Abstract

The R100Q mutation in the gamma-aminobutyric acid type A (GABA_A) receptor α₆ subunit was previously identified in Sardinian alcohol-preferring (sP) and Sardinian alcohol-nonpreferring (sNP) rats as a candidate gene influencing alcohol preference and sensitivity. The purpose of the current study was to determine to what extent this mutation and alcohol preference observed in the sP and sNP lines was present in other independently selected rat lines, including inbred alcohol-preferring (iP) and inbred alcohol-nonpreferring (iNP), high-alcohol-drinking 1 (HAD1) and low-alcohol-drinking 1 (LAD1), high-alcohol-drinking 2 (HAD2) and low-alcohol-drinking 2 (LAD2), and Alko Alcohol (AA) and Alko Non-Alcohol (ANA). Sequence analysis was first performed to screen for the R100Q mutation in several samples. Later, a genotyping assay was conducted to assess the frequency of the R100Q mutation in larger sample sizes. The R100Q mutation was identified only in the AA/ANA population, with a significantly (P<.0001) higher frequency in the alcohol-nonpreferring ANA line. The absence of the R100Q mutation in the other rat lines that were selectively bred for alcohol consumption and alcohol preference may be due to genetic diversity among the Wistar stocks used to develop the various lines.

Keywords: GABA_A receptor α₆ subunit, Polymorphism, Rat lines, Alcohol preference