title: AA and ANA rats exhibit the R100Q mutation in the GABAA receptor alpha 6 subunit.
abstract: The R100Q mutation in the gamma-aminobutyric acid type A (GABA(A)) receptor alpha(6) 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.
authors: Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. lcarr@iupui.edu
authors: Lucinda G
authors: LG
authors: Carr
authors: John P
authors: JP
authors: Spence
authors: C J
authors: CJ
authors: Peter Eriksson
authors: Lawrence
authors: L
authors: Lumeng
authors: Ting-Kai
authors: TK
authors: Li
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D001120:Arginine / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D005973:Glutamine / Q000235:genetics; D009154:Mutation; D051381:Rats; D011963:Receptors, GABA-A / Q000235:genetics*; D013045:Species Specificity
chemical_list: C546173:Gabra6 protein, rat; D011963:Receptors, GABA-A; D005973:Glutamine; D001120:Arginine