Osteopetrosis of microphthalmic mice—A defect of the hematopoietic stem cell?

Abstract

The recessive genesmi andgl in the homozygous state determine, among other phenotypic effects, osteopetrosis in the house mouse. From a stock carryingmi derived from Grüneberg (1963) themi gene was bred into the standard CBA/H inbred strain. Microphthalmic mice of these two stocks and their hybrids were treated as newborn by intraperitoneal injection and at weaning or maturity by intravenous injection of cell suspensions containing hematopoietic stem cells from phenotypically normal mice. Resolution of much of the osteopetrosis but not the other phenotypic effects occurred within a few months in the majority of cases, provided syngeneic or H-2 compatible allogeneic cells were given: it did not occur spontaneously or on giving H-2 incompatible cells or on giving compatible material by an inappropriate route. The results accord with hypotheses that (1) osteoclasis of scaffold-type woven bone is impaired inmi mi, (2) that osteoclastic cells are derived through circulating monocytes from hematopoietic stem cells, and (3) inmi mi this defect can be overcome by a transplant of normal hemopoietic stem cells.