Genetic mapping of social interaction behavior in B6/MSM consomic mouse strains

Abstract

Genetic studies are indispensable for understanding the mechanisms by which individuals develop differences in social behavior. We report genetic mapping of social interaction behavior using inter-subspecific consomic strains established from MSM/Ms (MSM) and C57BL/6J (B6) mice. Two animals of the same strain and sex, aged 10 weeks, were introduced into a novel open-field for 10 min. Social contact was detected by an automated system when the distance between the centers of the two animals became less than approximately 12 cm. In addition, detailed behavioral observations were made of the males. The wild-derived mouse strain MSM showed significantly longer social contact as compared to B6. Analysis of the consomic panel identified two chromosomes (Chr 6 and Chr 17) with quantitative trait loci (QTL) responsible for lengthened social contact in MSM mice and two chromosomes (Chr 9 and Chr X) with QTL that inhibited social contact. Detailed behavioral analysis of males identified four additional chromosomes associated with social interaction behavior. B6 mice that contained Chr 13 from MSM showed more genital grooming and following than the parental B6 strain, whereas the presence of Chr 8 and Chr 12 from MSM resulted in a reduction of those behaviors. Longer social sniffing was observed in Chr 4 consomic strain than in B6 mice. Although the frequency was low, aggressive behavior was observed in a few pairs from consomic strains for Chrs 4, 13, 15 and 17, as well as from MSM. The social interaction test has been used as a model to measure anxiety, but genetic correlation analysis suggested that social interaction involves different aspects of anxiety than are measured by open-field test.

Fig. 1

Social interaction behavior in B6 and MSM mice. a Duration (left side) and frequency (right side) of social contact. b Duration of detailed social interaction behavior (genital grooming, social sniffing, and following). Bars represent mean ± SEM. Asterisk indicates significant difference between B6 and MSM (P < 0.001)

Fig. 2

Social contact behavior in consomic mouse strains and B6. a Duration of social contact. Male and female data were combined because there was no strain-sex interaction. * P < 0.05 compared to B6. b Frequency of social contact in males and females. * Indicates significant differences with respect to the corresponding sex from B6 (P < 0.05). # Indicates significant sex differences within a strain (P < 0.05). The horizontal dotted line shows the mean for B6. MSM was excluded from the ANOVA analysis

Fig. 3

Detailed social interaction behavior in males from the consomic mouse strains and B6. a Genital grooming. b Social sniffing. c Following. The horizontal dotted line shows the mean for B6. Asterisks indicate significant differences as compared to B6 (P < 0.05). MSM was excluded from the ANOVA analysis

Fig. 4

Aggressive behavior in consomic strains and parental B6 and MSM. Figure shows the average duration of aggressive behavior (both attack and aggressive chasing) in animals that exhibited aggressive behavior. The numbers in parentheses show the number of pairs in each strain that showed aggressive behavior. Aggressive behavior was observed only in the five consomic strains shown in this figure