Experiment
A large set of ethological measures of anxiety-related behaviors were analyzed to explore the relationship between the behavioral phenotype and genotype of anxiety. Phenotypic and genotypic data from a total of 1636 mice from two intercosses of (H1 x L1)F2 and (H2 x L2) F2 DeFries strains decribed in a separate paper (J:70479) were obtained. Five behavorial tests were conducted in the open field arena, the elevated plus maze, the square maze, the light dark box and the mirror chamber. The test results from the two crosses were highly consistent and to maximize power and mapping resoultion the data was combined from both groups in the current study. Likely QTL positions were determined using MAPMAKER-QTL and QTL-CARTOGRAPHER.
The results of this study mapped 3 major QTL influencing anxiety-related behaviors on Chromosomes 1, 4 an 15. Other anxiety-related behavioral QTLs with multiple effects mapped to Chromosomes 7, 12, 14, 18 and X.
The major QTL mapping to Chromosome 15, Axtav, anxiety-avoidance behavior emerged with a profile most consistent with a role in anxiety. Its effects were almost entirely restricted to activity in anxiogenic compartments of the test apparatus. Genetic influence on latency measures were derived mostly from the Axtav.
The combined LOD scores from both crosses, for each significant test measurement contributing to Axtav follow:
anxiety-avoidance behavior, open field, total activity, LOD=12.5;
anxiety-avoidance behavior, open field, center activity, LOD=5.1;
anxiety-avoidance behavior, open field, center time, LOD=5.2;
anxiety-avoidance behavior, open field, latency to approach center LOD=9.0;
anxiety-avoidance behavior, elevated plus maze, open arm entries, LOD=13.0;
anxiety-avoidance behavior, elevated plus maze, open arm activity, LOD=11.8;
anxiety-avoidance behavior, elevated plus maze, open arm time, LOD=4.5
anxiety-avoidance behavior, elevated plus maze, latency to enter open arms, LOD=10.5;
anxiety-avoidance behavior, square maze, open arms activity, LOD=15.4;
anxiety-avoidance behavior, square maze, open arm entries, LOD=6.9;
anxiety-avoidance behavior, square maze, latency to enter open arms, LOD=4.6;
anxiety-avoidance behavior, light dark box, light box time, LOD=3.5;
anxiety-avoidance behavior, light dark box, light box activity, LOD=4.1;
anxiety-avoidance behavior, light dark box, transitions, LOD=13.5;
anxiety-avoidance behavior, light dark box, latency to emerge, LOD=19.6
anxiety-avoidance behavior, mirror chamber, latency to emerge, LOD=17.7
At each locus the direction of effect of the allele was examined from the less active strains, L1 and L2.
All traits measured at Axtav were decreased by the influence of the L1 or L2 allele with the exceptions of the latency loci:
anxiety-avoidance behavior, open field, latency to approach center,
anxiety-avoidance behavior, elevated plus maze, latency to enter open arms,
anxiety-avoidance behavior, square maze, latency to enter open arms,
anxiety-avoidance behavior, light dark box, latency to emerge, and
anxiety-avoidance behavior, mirror chamber, latency to emerge - all of which were increased by the low alleles L1 or L2. [Table 2].