Genetic architecture for hole-board behaviors across substantial time intervals in young, middle-aged and old mice

A quantitative trait locus (QTL) analysis of behaviors across the life span was conducted in F(2) mice from a C57BL/6J x DBA/2J cross and 22 BXD recombinant inbred (RI) strains. Mice of three age groups were tested in a hole-board apparatus for 3 min on three occasions approximately 1 month apart (average age at test 150, 450 and 750 days, approximately 400 mice per group, divided equally by sex). Quantitative trait loci with small effect size were found on 11 chromosomes for hole-board activity (Hbact) and hole-board rearing (Hbrear). Analysis of 22 RI strains tested at 150 and 450 days of age found only suggestive linkage, with four QTL for Hbact overlapping with those from the F(2) analysis. There was a significant phenotypic correlation between Hbact and Hbrear (approximately 0.55-0.69) and substantial commonality among QTL for the two behaviors. QTL analyses of head-pokes (HP) and fecal boli (FB) only identified QTL at the suggestive level of significance. Age accounted for approximately 15% of the phenotypic variance (sex approximately 3%), and there were genotype by age interactions at approximately 25% of the Hbact and Hbrear QTL. Quantitative trait loci for Hbrear were relatively stable across the three measurement occasions (those for Hbact somewhat less so), although mean levels of each index declined markedly comparing the first to subsequent trials. Considered as a whole, the polygenic system influencing exploratory behaviors accounts for approximately the same amount of phenotypic variance as age (within the range studied), is stable across substantial periods of time, and acts, for the most part, independently of age and sex.