@misc{oai:ir.soken.ac.jp:00001022,
 author = {西, 明紀 and ニシ, アキノリ and NISHI, Akinori},
 month = {2016-02-17},
 note = {In our laboratory, we have focused on the behavioral diversity of wild derived mouse strains. A wild derived mouse strain, MSM indicates prominent behavioral differences from C57BL/6J. These two strain belong to different subspecies. MSM and C57BL/6J belong to musculus subspecies group and domesticus subspecies group, respectively. There is a large amount of nucleotide differences between the two strains as it nearly reaches 1%. MSM is one of the most remote strains from C57BL/6J among inbred strains of mouse. Therefore, it is expected to obtain the new knowledge for behavioral mechanisms by comparing the two strains. To study the genetic factors associated with the behavioral diversity between the two strains, we used the consomic strains, otherwise known as chromosome substituted strains(CSS), derived from these two strains. The consomic strains were established by substitution of each one chromosome of C57BL/6J by the corresponding chromosome of MSM. These strains are discribed as B6-［chromosome nember]MSM. When only the centromere side or telomore side of a chromosomo derived from MSM is kept separately as two consomic strains, they are described as B6-[chromosome nember]CMSM or B6-[chromosome nember] TMSM, respectively. By using a series of consomic strains covering the whole genome,we are able to detect the quantitative trait loci(QTL) on each chromosome efficiently. Futhermore, consomic strains reduce the time and cost in establishing congenic strains that include the candidate QTL.<br />　　　In this study, I focused on two behavioral traits, general activity and emotionality. These two traits are the most basic behavioral traits across the animal species and important for animal to survive. It seemed that the basic mechanisms for both feneral activity and emotionality have been conserved in mammals. In human society, these traits deeply associate with personal quality of life (QOL). Abnormalities of these traits cause several serious psychiatric disorders. Because methods of studies for psychiatric disorders in human have limitation, approaches using rodent models have been applied for elucidating mechanisms for behaviral traits and psychiatric disorders. One of the most common approaches is analysis of knockout mouse, which has aberration on the gene associated with the focused mechanism (reverse genetics approach). By using this approach,roles of genes on the pathway related to the focused mechanism have been revealed and important knowledge for genetic factors associated with behavioral pathway has been accumulated. However, the mechanisms of the behavioral traits are complex and that many genetic and environmental factors are associated with the traits. Therefore, forward genetic approach, which focuses on the phenotype first and followed by analysis of the gene associated with the phenotype,has also been needed for understanding the genetic mechanism and genetic factors associated with behavioral traits.<br />　　　To evalute the behavioral traits of each consomic strain cyclopaedically, first, we established the behavioral test battery. In this study, I performed the novel cage test and the light dark box test to evaluate the emotionality and the home cage test to evaluate general activity for eighteen consomic strains, which cover about two-third of the entire chromosomes. In the result of behavioral tests, many strains showed behavioral differences from C57BL/6J. Interestingly,most of the consomic strains have own distinctive behavioral traits. When I sorted the behavioral traits of each consomic strains into categories of emotionality and general activity,for example, B6-7TMSM, B6-8MSM and B6-16MSM differed from C57BL/6J for general activity but not for emotionality. On the other hand, B6-1MSM,B6-2CMSM and B6-17MSM mainly increased anxiety related behavior than C57BL/6J. B6-6CMSM showed significantly great behavioral differences from C57BL/6J for both general activity and emotionality and emotionality related behavior. In total,seventeen out of eighteen tested strains showed some sort of behaviral differences from C57BL/6J. Through these behavioral tests, I successfully  characterized complex vehavioral traits by use of each consomic strain.<br />　　　Then, I characterized the behavioral phenotype of B6-6CMSM using multiple behavioral tests because this strain showed the biggest behavioral from C57BL/6J among the tested consomic strains. I evaluated the motor function, the emotionality related behavior and psychiatric disorders like phenotype using such as a rotarod test, a cued fear conditioning test and prepulse inhibition (PPI) test. In the result of these tests,B6-6CMSM did not have severe deficit for motor function in the rotarod test with constant slow speed while this strain showed the lower performance than C57BL/6J in the rotarod test with accelerated speed. B6-6CMSM had increased fear response in comparison with C57BL/6J in the fear conditioning test. There is no significant difference for psychiatric disorders like phenotype in the tail suspension test and the PPI test. Additionally, B6-6CMSM had higher dopamine level in striatum, which relates with behavioral activity,than C57BL/6J. On the other hand, the behavioral changes following injection of the depamine receptor agonist and dopamine transporter blocker were not different from those observed in C57BL/6J.<br />　　　In order to reveal the genetic factor associated with the behavioral phenotypes,I analyzed the QTLs on chromosome 6. I especially focused on genetic factors associated with the general activity and emotionlity. In the result of QTL analysis for the novel cage activity,activity in the light dark box and the home cage activity, I obtained mainly two QTLs. One QTL located in the centromere side(QTL-C) associated with the novel cage activity and activity in the light dark box. <br />Furthermore,the QTL-C was also associated with general activity for females ut not for males. The other QTL located in telomere side(QTL-T) was associated with only the home cage activity for both females and males. Therefore, it is suggested that different genes regulate emotionality and general activity of B6-6CMSM. The QTL-C mainly associates with emotionality of both sexes,and sex specific general activity. TheQTL-T regulates the general activity of both sexes. There are complex mechanisms associated with behavioral traits on chromosome 6. Therefore, I established a series of congenic strains for QTL by introducing shorter segment of chromosome 6 via meiotic recombination to narrow down the candidate regions.<br />　　　In this study, I obtained novel information for QTLs associated with multiple behavioral traits. I indicated the candidate regions associated with emotionality related traits and general activity of B6-6CMSM, and I was able to narrow down the candidate region associated with behavioral phenotype. I am expecting to understand the gene associated with behavioral traits by combing this QTL information, accumulated data for single nucleotide polymorphism between C57BL/6 and MSM and expression data of each gene., 総研大甲第959号},
 title = {A systematic analysis of genetic factors associated with behavioral traits by use of consomic mouse strains established from C57BL/6J and MSM/Ms},
 year = {}
}