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Titolo:
DEFICIENCY OF THE HCK AND SRC TYROSINE KINASES RESULTS IN EXTREME LEVELS OF EXTRAMEDULLARY HEMATOPOIESIS
Autore:
LOWELL CA; NIWA M; SORIANO P; VARMUS HE;
Indirizzi:
UNIV CALIF SAN FRANCISCO,DEPT MICROBIOL & IMMUNOL SAN FRANCISCO CA 94143 FRED HUTCHINSON CANC RES CTR,PROGRAM MOLEC MED SEATTLE WA 98104 NIH,OFF DIRECTOR BETHESDA MD 00000
Titolo Testata:
Blood
fascicolo: 5, volume: 87, anno: 1996,
pagine: 1780 - 1792
SICI:
0006-4971(1996)87:5<1780:DOTHAS>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXPRESS HIGH-LEVELS; SIGNAL-TRANSDUCTION; BONE-MARROW; PROTEIN-KINASES; STROMAL CELLS; MUTANT MICE; C-FOS; OSTEOCLASTS; FAMILY; OSTEOPETROSIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
45
Recensione:
Indirizzi per estratti:
Citazione:
C.A. Lowell et al., "DEFICIENCY OF THE HCK AND SRC TYROSINE KINASES RESULTS IN EXTREME LEVELS OF EXTRAMEDULLARY HEMATOPOIESIS", Blood, 87(5), 1996, pp. 1780-1792

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 inthe 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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Documento generato il 25/11/20 alle ore 10:17:30