Variants of kappa-opioid receptor gene and mRNA in alcohol-preferring and alcohol-avoiding mice.
Results of recent studies have indicated an association between voluntary alcohol intake and activities of kappa-opioid receptor systems in animal models. We assessed the possibility that genetic differences observed in alcohol preference among mouse strains are related to possible polymorphisms of the kappa-opioid receptor gene (Oprk1). We compared DNA sequences of the coding region and the promoter/regulatory region of Oprk1 among C57BL/6ByJ (B6, alcohol-preferring), BALB/cJ (alcohol-avoiding), CXBI (alcohol-avoiding), and six B6.C and B6.I Recombinant QTL Introgression (RQI) strains, which carry approximately 3% of the donor BALB/cJ genome in the background B6 genome and showed various alcohol preferences. Although there were no sequence differences in the coding region, BALB/cJ had a single nucleotide polymorphism (SNP) in the promoter region, which was not detected in other strains. The results indicate that the difference in alcohol preference between B6 and BALB/cJ is not correlated with polymorphisms of Oprk1. However, results of further studies comparing Oprk1 mRNA expression between B6 and BALB/cJ showed that Oprk1 expression is regulated differently in these strains. Also, DBA/2J mice (alcohol-avoiding) showed expression of Oprk1 mRNA subtypes (alternatively spliced) different from B6 and BALB/cJ mice. Search of the Celera Genomics database indicated that DBA/2J had several SNP sites in the promoter/regulatory regions, which might explain the different expression of Oprk1 mRNA subtypes in this strain. The strain-dependent variation in the expression of alternatively spliced genes can be a significant source of phenotypic variation of complex traits such as alcohol preference.
Saito
Mariko
M
Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA. Marasito@NKI.rfmh.org
Ehringer
Marissa A
MA
Toth
Reka
R
Oros
Melinda
M
Szakall
Istvan
I
Sikela
James M
JM
Vadasz
Csaba
C
D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001483:Base Sequence; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D017473:Receptors, Opioid, kappa / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity
D012333:RNA, Messenger; D017473:Receptors, Opioid, kappa; C116587:kappa(1) opioid receptor