Mapping of genetic factors that elicit intermale aggressive behavior on mouse chromosome 15: intruder effects and the complex genetic basis

Despite high estimates of the heritability of aggressiveness, the genetic basis for individual differences in aggression remains unclear. Previously, we showed that the wild-derived mouse strain MSM/Ms (MSM) exhibits highly aggressive behaviors, and identified chromosome 15 (Chr 15) as the location of one of the genetic factors behind this escalated aggression by using a panel of consomic strains of MSM in a C57BL/6J (B6) background. To understand the genetic effect of Chr 15 derived from MSM in detail, this study examined the aggressive behavior of a Chr 15 consomic strain towards different types of opponent. Our results showed that both resident and intruder animals had to have the same MSM Chr 15 genotype in order for attack bites to increase and attack latency to be reduced, whereas there was an intruder effect of MSM Chr 15 on tail rattle behavior. To narrow down the region that contains the genetic loci involved in the aggression-eliciting effects on Chr 15, we established a panel of subconsomic strains of MSM Chr 15. Analysis of these strains suggested the existence of multiple genes that enhance and suppress aggressive behavior on Chr 15, and these loci interact in a complex way. Regression analysis successfully identified four genetic loci on Chr 15 that influence attack latency, and one genetic locus that partially elicits aggressive behaviors was narrowed down to a 4.1-Mbp region (from 68.40 Mb to 72.50 Mb) on Chr 15.

尽管攻击性的遗传力估值颇高，但个体间攻击行为差异的遗传基础仍未明确。既往研究中，我们证实野生来源小鼠品系MSM/Ms（后文简称MSM）表现出极强的攻击行为，并通过以C57BL/6J（后文简称B6）为遗传背景的MSM染色体替换系（consomic strain）群体，将该加剧攻击行为的遗传位点之一定位于15号染色体（Chr 15）。为深入解析MSM来源的15号染色体的遗传效应，本研究针对不同类型的攻击对象，考察了15号染色体替换系小鼠的攻击行为。结果表明，仅当定居小鼠（resident animal）与入侵小鼠（intruder animal）均携带MSM来源的15号染色体基因型时，攻击咬击次数才会增多、攻击潜伏期才会缩短；而尾部震颤行为则仅受入侵小鼠携带的MSM 15号染色体的影响。为缩小15号染色体上参与诱发攻击行为的遗传位点区间，我们构建了MSM 15号染色体的亚染色体替换系（subconsomic strain）群体。对该群体的分析表明，15号染色体上存在多个可增强或抑制攻击行为的基因，且这些位点间存在复杂的互作关系。回归分析成功定位了15号染色体上影响攻击潜伏期的4个遗传位点，并将一个可部分诱发攻击行为的遗传位点缩小至15号染色体上4.1兆碱基对（Mbp）的区间内（68.40 Mb至72.50 Mb）。