The diagnosis and cure of neonatal osteopetrosis : experimental evidence from congenitally osteopetrotic ( ia) rats

Abstract

The phenotypic determination of osteopetrosis in incisors absent (ia) rats is made on the tenth day after birth, when the teeth fail to erupt in the mutants. The disease can be cured at this age by the transfer of spleen or thymus cells from a normal littermate to irradiated is animals. We sought to identify and treat newborn osteoteprotic rats without irradiation to eliminate the requirement for restoration of hematopoiesis during the cure of the disease. This would provide a direct means for investigating the precise cellular source of the cure. Using finegrain film and a point-source x-ray tube, newborn ia rats were identified radiographically by the absence of a marrow cavity in the femur. This criterion was validated by microscopic examination of long bones in 30 ia and normal rats. To test the ability of spleen cells to cure the disease in unirradiated hosts, 31 ia rats were given normal spleen cells, without irradiation on the day of birth and the progress of skeletal cure was monitored radiographically and histologically. The skeleton was completely remodeled by seven weeks. These results show that osteopetrosis can be identified in newborn ia rats and that cure of the disease can begin at this age.