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Genetic mapping of escalated aggression in wild-derived mouse strain MSM/Ms: association with serotonin-related genes
Aki Takahashi1, Toshihiko Shiroishi2, Tsuyoshi Koide1
1Mouse Genomics Resource Laboratory, National Institute of Genetics (NIG) Mishima, Japan ; Department of Genetics, SOKENDAI Mishima, Japan.
Abstract:
The Japanese wild-derived mouse strain MSM/Ms (MSM) retains a wide range of traits related to behavioral wildness, including high levels of emotionality and avoidance of humans. In this study, we observed that MSM showed a markedly higher level of aggression than the standard laboratory strain C57BL/6J. Whereas almost all MSM males showed high frequencies of attack bites and pursuit in the resident-intruder test, only a few C57BL/6J males showed aggressive behaviors, with these behaviors observed at only a low frequency. Sexually mature MSM males in their home cages killed their littermates, or sometimes female pair-mates. To study the genetic and neurobiological mechanisms that underlie the escalated aggression observed in MSM mice, we analyzed reciprocal F1 crosses and five consomic strains of MSM (Chr 4, 13, 15, X and Y) against the background of C57BL/6J. We identified two chromosomes, Chr 4 and Chr 15, which were involved in the heightened aggression observed in MSM. These chromosomes had different effects on aggression: whereas MSM Chr 15 increased agitation and initiation of aggressive events, MSM Chr 4 induced a maladaptive level of aggressive behavior. Expression analysis of mRNAs of serotonin receptors, serotonin transporter and Tph2, an enzyme involved in serotonin synthesis in seven brain areas, indicated several differences among MSM, C57BL/6J, and their consomic strains. We found that Tph2 expression in the midbrain was increased in the Chr 4 consomic strain, as well as in MSM, and that there was a strong positive genetic correlation between aggressive behavior and Tph2 expression at the mRNA level. Therefore, it is possible that increased expression of the Tph2 gene is related to escalated aggression observed in MSM.
Insights
The Japanese wild mouse strain MSM exhibits significantly higher aggression than laboratory mice. Genetic analysis identified chromosomes 4 and 15 as key contributors, potentially linked to Tph2 gene expression in the brain.
Area of Science:
- Neuroscience
- Behavioral Genetics
- Animal Models
Background:
- The MSM/Ms (MSM) mouse strain displays pronounced wild-type behaviors, including heightened emotionality and avoidance.
- MSM mice exhibit markedly elevated aggression compared to the standard C57BL/6J laboratory strain.
- Aggressive behaviors in MSM males include frequent attack bites, pursuit, and infanticide of littermates or mates.
Purpose of the Study:
- To investigate the genetic and neurobiological underpinnings of escalated aggression in MSM mice.
- To identify specific chromosomes and neurochemical pathways associated with heightened aggressive behavior.
Main Methods:
- Analysis of reciprocal F1 crosses between MSM and C57BL/6J mice.
- Examination of five consomic strains (MSM chromosomes 4, 13, 15, X, Y on a C57BL/6J background).
- Gene expression analysis of serotonin system components (receptors, transporter, Tph2) in seven brain regions.
Main Results:
- Chromosomes 4 and 15 were identified as significantly involved in MSM's heightened aggression.
- MSM Chr 15 influenced agitation and aggression initiation, while MSM Chr 4 induced maladaptive aggression.
- Increased Tph2 (tryptophan hydroxylase 2) gene expression in the midbrain correlated strongly with aggressive behavior in MSM and the Chr 4 consomic strain.
Conclusions:
- Chromosomes 4 and 15 play critical roles in regulating aggressive behavior in MSM mice.
- Elevated midbrain Tph2 expression is a potential neurobiological mechanism underlying the escalated aggression observed in MSM mice.
