AA and ANA rats exhibit the R100Q mutation in the GABAA receptor alpha 6 subunit.
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.
Carr
Lucinda G
LG
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. lcarr@iupui.edu
Spence
John P
JP
Peter Eriksson
C J
CJ
Lumeng
Lawrence
L
Li
Ting-Kai
TK
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
C546173:Gabra6 protein, rat; D011963:Receptors, GABA-A; D005973:Glutamine; D001120:Arginine