Advantage of Using Wild-Derived Mouse Strains for a Variety of Pain-Related Studies: Genetic Diversity and New Genetic Tools

KOIDE, TSUYOSHI; CATANESI, CECILIA INÉS; NISHI, AKINORI; SHIROISHI, TOSHIHIKO; KASAI, SHINYA; IKEDA, KAZUTAKA; TAKAHASHI, AKI

Acute Pain: Causes, Effects and Treatment

Nova Science Publishers, Inc.

Lugar: New York; Año: 2009; p. 79 - 99

Pain sensitivity has proved to be extremely variable among human individuals. One of the most important factors for such variations in pain-related phenomena is genetic diversity. A variety of mouse strains are reportedly suitable animal models for investigating the genetic basis of large individual differences in pain sensitivity. 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 pain-related phenotype studies is a great advantage. Several research groups have been involved in the long-term process of establishing a variety of wild-derived inbred strains from wild mice captured all over the world after at least 20 generations of brother-sister mating. The genetic diversity of wild-derived strains is advantageous for the analysis of phenotypic differences among strains. We previously identified a marked variety in pain and morphine sensitivity in a series of wild-derived inbred strains. In particular, we found that the MSM strain established from the Japanese wild mouse, Mus musculus molossinus, one of the subspecies of the musculus subspecies group, exhibits significant differences in pain-related phenotypes compared to C57BL/6 (B6). In order to study genetic factors associated with these differences, we used a panel of consomic strains, established by replacing each B6 chromosome by that of MSM on a B6 background. Our study identified multiple chromosomes related to reduced pain sensitivity in both hot-plate and tail-flick tests. Further mapping using subconsomic strains carrying a shorter segment of the chromosome allowed the successful characterization of a locus related with reduced pain sensitivity using the hot-plate test. Thus, this chapter reports on the usefulness of consomic strains for genetic analyses of pain-related phenotypes in mice. Editores: Sam D´Alonso and Katherine L. Grasso