1. ¹Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
2. ²Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA

Correspondence: Dr GD Gale, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California at Los Angeles, 23-120 CHS, Box 951735, Los Angeles, CA 90095-1735, USA. E-mail: ggale@mednet.ucla.edu

Received 23 July 2007; Revised 17 December 2007; Accepted 20 December 2007; Published online 1 April 2008.

Abstract

Understanding the genetics of behavioral variation remains a fascinating but difficult problem with considerable theoretical and practical implications. We used the genome-tagged mice (GTM) and an extensive test battery of well-validated behavioral assays to scan the genome for behavioral quantitative trait loci (QTLs). The GTM are a panel of 'speed congenic' mice consisting of over 60 strains spanning the entire autosomal genome. Each strain harbors a small (23 cM) DBA/2J donor segment on a uniform C57BL/6J background. The panel allows for mapping to regions as small as 5 cM and provides a powerful new tool for increasing mapping power and replicability in the analysis of QTLs. A total of 97 loci were mapped for a variety of complex behavioral traits including hyperactivity, anxiety, prepulse inhibition, avoidance and conditional fear. A larger number of loci were recovered than generally attained from standard mapping crosses. In addition, a surprisingly high proportion of loci, 63%, showed phenotypes unlike either of the parental strains. These data suggest that epistasis decreases sensitivity of locus detection in traditional crosses and demonstrate the utility of the GTM for mapping complex behavioral traits with high sensitivity and precision.