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

Abstract

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.

The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference

“…High impulsivity was found in 5-HT 2B mutant ( Htr2b −/− ) mice [ 161 ]. Among the QTLs underlying behaviors associated with intermale aggression in mice, the strongest candidate within the narrow QTL interval on chromosome 1 for both attack and latency variables is Htr2b gene [ 162 ].…”

Effects of kinship correction on inflation of genetic interaction statistics in commonly used mouse populations

“…We selected these populations to represent a range of relatedness and population structure. The populations were as follows: a reciprocal backcross ( Reifsnyder et al 2000 ), an F2 intercross ( Tyler et al 2016 ), a panel of BXD RILs ( Delprato et al 2015 , 2017 , 2018 ), a cohort of Diversity Outbred mice ( Svenson et al 2012 ; Tyler et al 2017 ), and a cohort from an AIL ( Hernandez Cordero et al 2018 ). We created a sixth study population by averaging over genomic replicates in the RIL.…”

“…The data we analyzed were from an experiment investigating the genetics of hippocampal anatomy and spatial learning ( Delprato et al 2015 , 2017 , 2018 ). The data set is called Crusio1.…”

Neuropsychological Approach to the Problem of Aggressive Manifestations of Personality

“…Genetic predisposition to aggressive behavior and its neurobiological factors are successfully studied by modern foreign experts (Bortolato et al, 2011;Delprato et al, 2018). Like most biological factors, hormones do not act independently of the social context, which has a significant impact on the manifestation of aggressiveness.…”