References
Query Results -- Details
MGI Accession ID: MGI:79133
J Number: J:31647
Other Accession IDs:
Title: Deficiency of the Hck and Src tyrosine kinases results in extreme levels of extramedullary hematopoiesis.
Authors: Lowell CA; Niwa M; Soriano P; Varmus HE
Journal: Blood
Volume: 87
Issue: 5
Date: 1996 Mar 1
Year: 1996
Pages: 1780-92
Review Status: Peer Reviewed
Abstract:
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.
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