Variants of κ-opioid receptor gene and mRNA in alcohol-preferring and alcohol-avoiding mice

Saito, Mariko; Ehringer, Marissa A.; Toth, Reka; Oros, Melinda; Szakall, Istvan; Sikela, James M.; Vadasz, Csaba

« Previous Next »Alcohol
Volume 29, Issue 1 , Pages 39-49, January 2003

Variants of κ-opioid receptor gene and mRNA in alcohol-preferring and alcohol-avoiding mice☆

Mariko Saito
- Corresponding author. Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA. Tel.: +1-845-398-5537; fax: +1-845-398-5531.
- Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
- Department of Psychiatry, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA
Marissa A. Ehringer
- Department of Pharmacology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA
- Human Medical Genetics Program, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA
Reka Toth
- Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
Melinda Oros
- Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
Istvan Szakall
- Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
James M. Sikela
- Department of Pharmacology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA
- Human Medical Genetics Program, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA
Csaba Vadasz
- Laboratory of Neurobehavior Genetics, The Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA
- Department of Psychiatry, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA

Received 26 July 2002; received in revised form 4 October 2002; accepted 17 October 2002.

Abstract

Results of recent studies have indicated an association between voluntary alcohol intake and activities of κ-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 κ-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 ∼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.

Keywords: κ opioid receptor gene, Oprk1, Alcohol preference, Single nucleotide polymorphisms, mRNA expression, DNA sequencing, C57BL/6ByJ, BALB/cJ, DBA/2J, Alternative splicing