| First Author | Lowell CA | Year | 1996 |
| Journal | Blood | Volume | 87 |
| Issue | 5 | Pages | 1780-92 |
| PubMed ID | 8634424 | Mgi Jnum | J:31647 |
| Mgi Id | MGI:79133 | Doi | 10.1182/blood.v87.5.1780.1780 |
| Citation | Lowell CA, et al. (1996) Deficiency of the Hck and Src tyrosine kinases results in extreme levels of extramedullary hematopoiesis. Blood 87(5):1780-92 |
| abstractText | Expression of the Src-family kinases-Src, Hck, and Fgr- 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 hck-/- or fgr-/- mice have few and subtle myeloid cell deficiencies. To determine whether these limited phenotypes are due to the coexpression of multiple Src- family kinases with overlapping functions, we have intercrossed src(-/-) mice to hck(-/-) and fgr(-/-) 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, and leukopenia. These hematopoietic defects are caused by abnormalities in the bone marrow environment because hck(-/-)src(-/-) mutant stem cells reconstitute a normal hematopoietic system in irradiated wild-type mice. In contrast, fgr(-/-)src(-/-) double mutants have no defects beyond those observed in src(-/-) animals. Cultured normal murine osteoclasts express abundant amounts of Src, Hck, and Fgr and Hck levels are increased in src(-/-) osteoclasts. These observations suggest that Hck and Src serve partially overlapping functions in osteoclasts and that the expression of Hck in src-/- osteoclasts ameliorates their functional defects. (C) 1996 by The American Society of Hematology. |
