Bone metabolism in the osteopetrotic rat mutation microphthalmia blanc.

We have examined parameters of bone metabolism in a new mutation, microphthalmia blanc (mib), in the rat exhibiting a skeletal sclerosis at birth that improves with age. There were no significant differences in the rate of bone formation during the first postnatal month except a temporary reduction in mutants at 3 weeks that coincided with compromised nutrition at weaning. At birth the ruffled border in mutant osteoclasts was absent or poorly developed and mRNA analyses of mutant bone compared to normal bone showed significant reductions in the messages for the osteoclast-specific genes carbonic andydrase II and tartrate-resistant ATPase. These distinctive ultrastructural and molecular differences were not present 1 month later. These data show that the transient osteopetrosis in mib rats results from a perinatal reduction in ultrastructural and enzymatic features of active osteoclasts and is not complicated by elevations in bone formation. The molecular basis for both the production and resolution of these abnormalities deserves further study.