Quantitative trait loci for novelty/stress-induced locomotor activation in recombinant inbred (RI) and recombinant congenic (RC) strains of mice

Abstract

The objective of the present study was to map and compare quantitative trait loci (QTLs) for an anxiety-related trait (novelty/stress-induced activation) in the AXB/BXA recombinant inbred (RI) and AcB/BcA recombinant congenic (RC) strains of mice derived from the A/J and C57BL/6J inbred progenitor strains. Activational responses to a novel open field (OF) were measured under identical stressful conditions (no prior handling or exposure to testing procedures) in both the RI and RC strains. Naive male and female mice were weighed, injected with IP saline and locomotor activity was monitored in a computerized OF apparatus for 15 min. Measures obtained from this experimental design included: (1) total activity scores, (2) time course of response (5 min time blocks over the 15 min session). Data for the RI strains were subjected to a QTL analysis using composite interval mapping. Significant loci were identified on chr 5 ( D5Mit356, 41 cM), chr 8 ( D8Mit305, 37 cM) and chr 14 ( D14Mit36, 63 cM). Single locus association analysis of the AcB/BcA RC strains identified 15 putative regions, 7 of which overlapped regions independently mapped in the RI strains on chr 1 (58.5–63.1 cM), chr 4 (21.9–28.6 cM), chr 5 (19–45 & 74–86 cM), chr 6 (0.5–20.4 cM), chr 9 (15–38 cM), chr 13 (47 cM) and chr 19 (47 cM). The loci identified on chr 5 near D5Mit356 (41 cM) in both the AXB/BXA RIS and AcB/BcA RCS maps to a region containing the genes for several GABA A receptor subunits. Additionally, the present study provides further confirmation of a frequently identified QTL on chromosome 1. The results are discussed in the context of previous QTL studies of anxiety-related traits that have used genetic crosses that include the A or B6 progenitors.