Lisa M. Tarantino 1,2,4 & Gerald McClearn1,2,3,4
A substantial body of literature has addressed genetic factors in predisposition to alcoholism. Genetic studies in humans are, of course, confounded by other factors such as environmental and social circumstances. Animal models offer a more direct way of studying the genetic influences on alcohol-related processes while controlling for these other factors. It was discovered in the 1950s that inbred strains of mice differ in voluntary consumption of alcohol (McClearn & Rodgers, 1959, Q J Stud Alcohol 20, 691-695). Since then, researchers have capitalized on the differences between two of these strains, C57BL/6 and DBA/2, in an effort to gain an understanding of the genetic factors underlying alcohol-related behaviors. Utilizing BXD recombinant inbred (RI) mice, we have previously nominated several chromosomal regions, called quantitative trait loci (QTLs), which may contain genes associated with alcohol consumption (Rodriguez et al., 1995, Alcohol Clin Exp Res 19, 367-373). This study was the first step in a multi-stage research program which included subsequent analysis of an F2 intercross population to confirm the nominated regions. Four of these regions have been replicated (Tarantino et al., in press, Alcohol Clin Exp Res). We have recently completed a genotypic selection experiment for two of the regions on Chrs 2 and 4. The Chr 2 QTL has replicated again while the Chr 4 QTL, although in the right direction, did not yield a significant result. We have also analyzed 218 F4 animals in an attempt to narrow the regions implicated in both the RI and F2 study. Once again we have replicated the results from previous studies while also indicating that even an early generation of an advanced intercross can narrow QTL regions significantly.
Address: 101 Amy Gardner Building, University Park, PA 16802; Ph: 814-865-1717;, Fax: 814-863-4768; e-mail: lisa@maustrap.cdhg.psu.edu
1Center for Developmental and Health Genetics, 2Intercollege Graduate Program in Genetics 3Department of Biobehavioral Health 4The Pennsylvania State University 5Funding provided by AA-08125 and DA-07277