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Deficiency of the Hck and Src tyrosine kinases results in extreme levels of
extramedullary hematopoiesis
CA Lowell, M Niwa, P Soriano and HE Varmus
Department of Microbiology and Immunology, University of California, San
Francisco, USA.
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.
Volume 87,
Issue 5,
pp. 1780-1792,
03/01/1996
Copyright © 1996 by The American Society of Hematology
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|
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