Spontaneous mutation in Mitf gene causes osteopetrosis in silver homozygote quail.

Silver homozygous quail was recently reported to have mutations in Mitf gene. Although numerous mutations in Mitf gene have been reported in mice, no mutations corresponding to the mutation in the homozygous silver (B/B) quail in Mitf gene have been reported to cause defects in pigmentation and bone. Therefore, we investigated the bones of the B/B homozygotes. Comparison of the bones of the B/B homozygotes with those of wild-type by X-ray examination revealed osteopetrosis in the long bones of B/B homozygotes. However, osteopetrosis in B/B homozygotes was less severe than that observed in mi/mi mice. Histological examination showed that there were less TRAP-positive multinucleated cells in the trabecular bones in B/B homozygote tibia than in the wild type. In vitro osteoclastogenesis study also suggested that formation of TRAP-positive multinucleated cell was suppressed in the marrow cells of the long bones of the B/B homozygotes. Furthermore, overexpression of chicken Mitf via retroviral transfection into B/B homozygote bone marrow cells in cultures increased the number of TRAP-positive cells 2-3 fold more than that in control. These results indicated that in addition to the previously reported defect in melanogenesis, osteoclastogenesis was inhibited in B/B homozygotes. These results indicate that the novel mutations in Mitf gene observed in the B/B homozygote quail impair osteoclastic bone resorption.