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Mouse Genomics Resource Laboratory (MGRL)

Behavior Genetics in Mouse Genomics Resource Laboratory (MGRL)

Much of the genetic variation that underlies most behavioral traits is complex and is regulated by loci (QTL) that have a quantitative effect on the phenotype. The aim of our study is to uncover the genetic architecture underlying individual differences of behavior in animals.

Laboratory strains have been reported to exhibit different behavioral traits due to variations in their genetic background. However, they show low genetic polymorphism because the original colony bred to produce the strains comprises a relatively low number of mice belonging to the subspecies Mus musculus domesticus. The low heterogeneity of laboratory strains makes their behavioral phenotype less variable. Therefore, the use of inbred strains derived from different mouse subspecies for behavioral studies is a great advantage.

Several research groups have been involved in the long-term process of establishing a variety of wild inbred strains from wild mice captured all over the world after at least 20 generations of brother-sister mating. The genetic diversity of wild strains is advantageous for the analysis of phenotypic differences among strains. We previously identified a marked variety in behavioral phenotype in a series of wild strains (Koide et al. 2000). In particular, we found that the MSM/Ms (MSM) strain established from the Japanese wild mouse, Mus musculus molossinus, one of the subspecies of the musculus subspecies group, exhibits significant differences in a series of behavioral phenotypes compared to C57BL/6 (B6) and still retain several behavioral characters of wild mice.

In order to reveal roles of genes in behavior, we are conducting genome editing using CRISPR/Cas9 system. By using this new technique, we are now trying to show how genomic polymorphisms affect behavior. 

Tameness and wildness

Humans have developed many domestic animals for various purposes. Tameness is a behavioral characteristic that is changed during domestication process of wild ancestors. However, it is still need to be clarified how tameness change the behavior of animals. In this point of view, we took particular note of a book written by an American zoologist, Edward O. Price. He defined tameness as “a measure of the extent to which an individual is reluctant to avoid or motivated to approach humans.” In order to address this point, we developed three behavioral tests to measure the level of two different classes of tameness in mice. We characterized tame behavior using 17 inbred mouse strains: ten wild strains, one Japanese fancy-mouse strain, and six laboratory strains. As a results, most of the domesticated strains showed significantly greater reluctance to avoid humans than wild strains, whereas there was no significant difference in the level of motivation to approach humans between these two groups.  These results suggest that domesticated strains were predominantly selected for reluctance to avoid humans over the course of their domestication history. We are currentry trying to understand the genetic basis of tameness using new mouse resource established from wild strains.

Social Behavior

Social behavior has essential role for most animal species. However, genetic mechanisms underlying the individual differences of social behavior have been not well understood because this behaviour is influenced by social interactions between multiple animals. Therefore, genetic analysis of social behavior between same-genotype animals may be more sensitive way as this method will be able to detect both active and passive social behavior as well as interactive enhancement and inhibition caused between same genotype animals. In this respect, consomic strains will be favorable resources to perform genetic mapping of loci related to the social interaction behaviour. We mapped QTLs related to social behavior using a panel of consomic strains (Takahashi et al. 2010 in press). Wild strain MSM was highly interactive and showed aggressive behavior in the neutral encounter situation. Analysis of consomic panel of mice revealed multiple chromosomes associated with enhancement and inhibition of social interaction and aggressive behavior. Increased aggression in consomic strain of Chr 15 (B6-Chr15MSM) was confirmed in the resident-intruder test. We are crrently doing further study to isolate causative genes related to these phenotype. 

Anxiety-Related Behavior

We have been working on genetic architecture underlying anxiety-related behavior by using consomic strains of mice. We found that B6-Chr17MSM, which carries Chr 17 from MSM/Ms, showed increased risk-assessment in the novel situation, increased fear response in the fear-conditioning test, but no differences in their home-cage activity compared to B6. Thus, it is expected that there is a genetic locus or loci associated with emotionality on Chr 17. We are currently trying to identify a gene related to the anxiety-related phenotype.

Spontaneous Home-cage Activity

Spontaneous home-cage activity of mice is regulated by complex genetic mechanism. We have analyzed consomic strains to elucidate genetic mechanism responsible for spontaneous activity and now trying to find genes responsible for different level of home-cage activity.

Bitter-taste sensitivity

Sucrose octaacetate (SOA) is a bitter tastant for many animal species. Aversion to SOA in laboratory mice is controlled by multigenic factors. We have studied the MSM and MSM consomic strains on a B6 host background.  Using two-bottle preference procedures, MSM mice avoided 0.1 mM and 1 mM SOA while B6 mice were indifferent to 0.1 mM and exhibited slight aversion to 1 mM SOA.  Two-bottle preference using a panel of consomic strains showed chromosomes 2, 4 and 15 showed moderate SOA aversion in addition to the prominent effect of the known Soa locus on chromosome 6.  The originally defined Soa locus is presumably associated with one or more members of the cluster of Tas2r genes on distal chromosome 6 that code for bitter taste receptors. We are currently trying to identify Tas2r gene which is critical for SOA aversion by using a calcium-imaging method.

National Institute of Genetics    | | ©2005 Tsuyoshi Koide    Last update 2016 April