Spontaneous mutation in Mitf gene causes osteopetrosis in silver homozygote quail

Silver homozygous quail was recently reported to have mutations in Mitf gen e. Although numerous mutations in Mitf gene have been reported in mice, no mutations corresponding to the mutation in the homozygous silver (BIB) quai l in Mitf gene have been reported to cause defects in pigmentation and bone . Therefore, we investigated the bones of the B/B homozygotes, Comparison o f the bones of the B/B homozygotes with those of wild-type by X-ray examina tion revealed osteopetrosis in the long bones of BIB homozygotes, However, osteopetrosis in BIB homozygotes was less severe than that observed in mi/m i mice. Histological examination showed that there were less TRAP-positive multinucleated cells in the trabecular bones in BIB homozygote tibia than i n the wild type. In vitro osteoclastogenesis study also suggested that form ation of TRAP-positive multinucleated cell was suppressed in the marrow cel ls of the long bones of the BIB homozygotes, Furthermore, overexpression of chicken Mitf via retroviral transfection into BIB homozygote bone marrow c ells 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 prev iously reported defect in melanogenesis, osteoclastogenesis was inhibited i n BIB homozygotes, These results indicate that the novel mutations in Mitf gene observed in the B/B homozygote quail impair osteoclastic bone resorpti on. (C) 2001 Wiley-Liss, Inc.