Biased suppression of hematopoiesis and multiple developmental defects in chimeric mice containing Shp-2 mutant cells

Cheng Kui Qu, Wen Mei Yu, Biagio Azzarelli, Scott Cooper, Hal Broxmeyer, Gen Sheng Feng

Research output: Contribution to journalArticle

105 Citations (Scopus)

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 in the 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, and pathological changes in the lungs, intestines, and skin. These results demonstrate a functional involvement of Shp-2 in the differentiation of multiple tissue-specific cells and in body organization. More importantly, the requirement for Shp-2 is more stringent in hematopoiesis than in other systems.

Original languageEnglish
Pages (from-to)6075-6082
Number of pages8
JournalMolecular and Cellular Biology
Volume18
Issue number10
StatePublished - 1998

Fingerprint

Hematopoiesis
Embryonic Stem Cells
Colony-Forming Units Assay
Myeloid Progenitor Cells
Lumbar Vertebrae
Yolk Sac
Erythroid Precursor Cells
Wild Animals
src Homology Domains
Sequence Deletion
Receptor Protein-Tyrosine Kinases
Ribs
Phosphoric Monoester Hydrolases
Intestines
Tyrosine
Cell Differentiation
Blood Cells
Leg
Embryonic Structures
Extremities

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Biased suppression of hematopoiesis and multiple developmental defects in chimeric mice containing Shp-2 mutant cells. / Qu, Cheng Kui; Yu, Wen Mei; Azzarelli, Biagio; Cooper, Scott; Broxmeyer, Hal; Feng, Gen Sheng.

In: Molecular and Cellular Biology, Vol. 18, No. 10, 1998, p. 6075-6082.

Research output: Contribution to journalArticle

Qu, Cheng Kui ; Yu, Wen Mei ; Azzarelli, Biagio ; Cooper, Scott ; Broxmeyer, Hal ; Feng, Gen Sheng. / Biased suppression of hematopoiesis and multiple developmental defects in chimeric mice containing Shp-2 mutant cells. In: Molecular and Cellular Biology. 1998 ; Vol. 18, No. 10. pp. 6075-6082.
@article{c355a7a5aaf04ba8b88a9035910817e3,
title = "Biased suppression of hematopoiesis and multiple developmental defects in chimeric mice containing Shp-2 mutant cells",
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 in the 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, and pathological changes in the lungs, intestines, and skin. These results demonstrate a functional involvement of Shp-2 in the differentiation of multiple tissue-specific cells and in body organization. More importantly, the requirement for Shp-2 is more stringent in hematopoiesis than in other systems.",
author = "Qu, {Cheng Kui} and Yu, {Wen Mei} and Biagio Azzarelli and Scott Cooper and Hal Broxmeyer and Feng, {Gen Sheng}",
year = "1998",
language = "English",
volume = "18",
pages = "6075--6082",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "10",

}

TY - JOUR

T1 - Biased suppression of hematopoiesis and multiple developmental defects in chimeric mice containing Shp-2 mutant cells

AU - Qu, Cheng Kui

AU - Yu, Wen Mei

AU - Azzarelli, Biagio

AU - Cooper, Scott

AU - Broxmeyer, Hal

AU - Feng, Gen Sheng

PY - 1998

Y1 - 1998

N2 - 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 in the 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, and pathological changes in the lungs, intestines, and skin. These results demonstrate a functional involvement of Shp-2 in the differentiation of multiple tissue-specific cells and in body organization. More importantly, the requirement for Shp-2 is more stringent in hematopoiesis than in other systems.

AB - 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 in the 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, and pathological changes in the lungs, intestines, and skin. These results demonstrate a functional involvement of Shp-2 in the differentiation of multiple tissue-specific cells and in body organization. More importantly, the requirement for Shp-2 is more stringent in hematopoiesis than in other systems.

UR - http://www.scopus.com/inward/record.url?scp=0031708674&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031708674&partnerID=8YFLogxK

M3 - Article

VL - 18

SP - 6075

EP - 6082

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 10

ER -