Skeletal biology in the toothless (osteopetrotic) rat

The toothless (tl) rat is a nonlethal osteopetrotic mutation characterized by the presence of few osteoclasts and the failure to be cured by bone-marrow transplantation. We examined the skeletal biology of tl rats and normal littermates up to 6 weeks after birth. Osteoclasts in tl rats were small, reduced 25-fold in number, and had greatly reduced concentrations of acid hydrolases. Bone shape internally and externally reflected reduced bone resorption, and tl rats were hypophosphatemic and mildly hypocalcemic at 2 weeks. These data indicate that the basic defect in tl rats is one of differentiation of osteoclasts and, coupled with the observation that normal bone-marrow cells cannot develop into osteoclasts in the tl skeleton, suggest that the defect lies in the skeletal micro-environment.