Deficiency of the Hck and Src Tyrosine Kinases Results in Extreme Levels

increases dramatically during myeloid cell development. Src-deficient mice exhibit functional abnormalities in only one myeloid cell type, the osteoclast, resulting in impaired bone remodeling and osteopetrosis, while he&-‘- or fgi ’-mice have few and subtle myeloid cell deficiencies. To deter-mine whether these limited phenotypes are due to the coex-pression of multiple Sic-family kinases with overlapping functions, we have intercrossed src-l- mice to hck-l- and fgr-l- mutants to produce double mutants. Two thirds of hck-’-src-’- double mutants die at birth; surviving animals develop a severe form of osteopetrosis, resulting in extreme levels of splenic extramedullary hematopoiesis, anemia, HE Src family of protein tyrosine kinases has been im- T plicated in a wide variety of intracellular signaling pathways in hematopoietic cells. Each hematopoietic cell lineage expresses multiple members of the Src family.’,2 Th