THE DEVELOPMENT AND ESTABLISHMENT OF HEMATOPOIESIS IN FETAL AND NEWBORN OSTEOPETROTIC (OP OP) MICE/

Previous studies of young CSF-1-less osteopetrotic (op/op) mice demons trate a severe deficiency of both macrophages and osteoclasts, resulti ng in excessive bone formation, occlusion of the marrow cavity, and re duced hemopoietic activity. The accompanying splenomegaly and prolonge d splenic hemopoiesis observed in these mice suggests that osteopetros is may perturb the normal progression of fetal hemopoietic development and obstruct the seeding of hemopoietic precursors into the bone marr ow. This study demonstrates that the absence of CSF-1 does not affect the progression of hemopoietic development in fetal op/op mice until a fter colonization of the bone marrow. Significant deficiencies in marr ow cellularity and progenitor cell content in the long bones of op/op mice were not evident prior to Day 2 postnatal, suggesting that the al tered hemopoietic state of young op/op mice is not a consequence of ab normal fetal hemopoietic development, but is primarily due to the lack of functional osteoclasts in op/op fetuses and hence, impaired remode ling of the marrow cavity after birth. (C) 1994 Academic Press, Inc.