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Titolo:
BIASED SUPPRESSION OF HEMATOPOIESIS AND MULTIPLE DEVELOPMENTAL DEFECTS IN CHIMERIC MICE CONTAINING SHP-2 MUTANT-CELLS
Autore:
QU CK; YU WM; AZZARELLI B; COOPER S; BROXMEYER HE; FENG GS;
Indirizzi:
INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,1044 W WALNUT ST,ROOM 302 INDIANAPOLIS IN 46202 INDIANA UNIV,SCH MED,WALTHER ONCOL CTR INDIANAPOLIS IN 46202 INDIANA UNIV,SCH MED,DEPT BIOCHEM & MOL BIOL INDIANAPOLIS IN 46202 INDIANA UNIV,SCH MED,DEPT PATHOL & LAB MED INDIANAPOLIS IN 46202 INDIANA UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL INDIANAPOLIS IN 46202 WALTHER CANC INST INDIANAPOLIS IN 46208
Titolo Testata:
Molecular and cellular biology
fascicolo: 10, volume: 18, anno: 1998,
pagine: 6075 - 6082
SICI:
0270-7306(1998)18:10<6075:BSOHAM>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
EMBRYONIC STEM-CELLS; SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; PROTEIN-TYROSINE-PHOSPHATASE; TRANSCRIPTION FACTOR GATA-1; IN-VITRO DIFFERENTIATION; SIGNAL-TRANSDUCTION; TARGETED MUTATION; SYP PHOSPHATASE; KINASE; GENE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
41
Recensione:
Indirizzi per estratti:
Citazione:
C.K. Qu et al., "BIASED SUPPRESSION OF HEMATOPOIESIS AND MULTIPLE DEVELOPMENTAL DEFECTS IN CHIMERIC MICE CONTAINING SHP-2 MUTANT-CELLS", Molecular and cellular biology, 18(10), 1998, pp. 6075-6082

Abstract

Shp-2 is a cytoplasmic tyrosine phosphatase that contains two Src homology 2 (SH2) domains at the N terminus. Biochemical data suggests that Shp-2 acts downstream of a variety of receptor and cytoplasmic tyrosine kinases. A targeted deletion mutation in the N-terminal SH2 (SH2-N) domain results in embryonic lethality of homozygous mutant mice at midgestation. In vitro embryonic stem (ES) cell differentiation assays suggest that Shp-2 might play an important role in hematopoiesis. By aggregating homozygous mutant (Shp2(-/-)) ES cells and wild-type (WT) embryos, we created Shp-2(-/-)-WT chimeric animals. We report here an essential role of Shp-2 in the control of blood cell development. Despite the widespread contribution of mutant cells to various tissues, no Shp-2(-/-) progenitors for erythroid or myeloid cells were detected inthe fetal liver and bone marrow of chimeric animals by using the in vitro CFU assay. Furthermore, hematopoiesis was defective in Shp-2(-/-)yolk sacs. In addition, the Shp-2 mutation caused multiple developmental defects in chimeric mice, characterized by short hind legs, aberrant limb features, split lumbar vertebrae, abnormal rib patterning, andpathological changes in the lungs, intestines, and skin. These results demonstrate a functional involvement of Shp-2 in the differentiationof multiple tissue-specific cells and in body organization. More importantly, the requirement for Shp-2 is more stringent in hematopoiesis than in other systems.

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Documento generato il 05/04/20 alle ore 06:34:57