Bone Density Analysis Of The Small Body Size Mouse And Mapping Of The Mutant Gene

The mutant mouse which showed dwarfism was developed by iV-ethyl-N-nitrosoure (ENU) mutagenesis in BALB/c mice. The mutant mouse was inherited as autosomal recessive trait and named Small Body Size (SBS) mouse. The phenotype of SBS mouse was not apparent at birth, however it was possible to distinguish mutant from normal mice after 1 week of age. In this study, we examined body weight changes and bone mineral density (BMD) and we also carried out genetic linkage analysis to map the causative gene of SBS mouse. Body weight changes were observed from birth to 14 weeks of age in both affected (n=30) and normal mice (n=24). BMD was examined in each five SBS and normal mice between 3 and 6 weeks of age, respectively. For the linkage analysis, we produced backcross progeny [(SBS × C57BL/6J)F₁ × SBS]N₂ mice (n=142), and 79 microsatellite markers were used for linkage analysis. Body weight of affected mice was consistently lower than that of the normal mice, and was 43.7% less than that of normal mice at 3 weeks of age (P < 0.001). As compared with normal mice, BMD of the SBS mice was significantly low. The causative gene was mapped on Chromosome 10. After selectively amplifying the marker D10Mit283 that was most proximal to Pbw--g9 gene and Pex7 gene that related to the dwarfi-sm phenotype on the chromosome 10, only one exchange was found among 142 F₂ generation mice. Pbwg9 gene and Pex7 gene were considered as strong candidate gene for the dwarfism phenotype.