A quantitative trait locus on chromosome 1 modulates intermale aggression in mice

Aggression between male conspecifics is a complex social behavior that is likely modulated by multiple gene variants. In this study, the BXD recombinant inbred mouse strains (RIS) were used to map quantitative trait loci (QTLs) underlying behaviors associated with intermale aggression. Four hundred and fifty-seven males from 55 strains (including the parentals) were observed at an age of 13 ± 1 week in a resident-intruder test following 10 days of isolation. Attack latency was measured directly within a 10-minute time period and the test was repeated 24 hours later. The variables we analyzed were the proportion of attacking males in a given strain as well as the attack latency (on days 1 and 2, and both days combined). On day 1, 29% of males attacked, and this increased to 37% on day 2. Large strain differences were obtained for all measures of aggression, indicating substantial heritability (intraclass correlations 0.10-0.18). We identified a significant QTL on chromosome (Chr) 1 and suggestive QTLs on mouse Chrs 1 and 12 for both attack and latency variables. The significant Chr 1 locus maps to a gene-sparse region between 82 and 88.5 Mb with the C57BL/6J allele increasing aggression and explaining about 18% of the variance. The most likely candidate gene modulating this trait is Htr2b which encodes the serotonin 2B receptor and has been implicated in aggressive and impulsive behavior in mice, humans and other species.