Requirement of Shp-2 tyrosine phosphatase in lymphoid and hematopoietic cell development

• Published in: Blood Vol. 97; no. 4; pp. 911 - 914
• Main Authors: QU, Cheng-Kui, NGUYEN, Suzanne, JIANZHU CHEN, FENG, Gen-Sheng
• Format: Journal Article
• Language: English
• Published: Washington, DC The Americain Society of Hematology 15.02.2001
• Subjects: Animals; B-Lymphocytes - cytology; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell Lineage; Cell physiology; Chimera; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; Embryonic and Fetal Development - genetics; Female; Fundamental and applied biological sciences. Psychology; Genetic Complementation Test; Genotype; Hematopoiesis - genetics; Hematopoiesis - physiology; Hematopoietic Stem Cells - enzymology; Immunologic Deficiency Syndromes - genetics; Lymphocytes - cytology; Lymphocytes - enzymology; Mice; Mice, Knockout; Molecular and cellular biology; Phosphorylation; Protein Processing, Post-Translational; Signal Transduction; Specific Pathogen-Free Organisms; T-Lymphocytes - cytology; Yolk Sac - cytology; Embryonic development; Animal model; Lymphoid cell; Lymphopoiesis; Enzyme; Phosphoprotein phosphatase; Stem cell; Rodentia; Precursor cell; Phosphoric monoester hydrolases; Hematopoietic cell; Esterases; Vertebrata; Regulation(control); Mammalia; Mouse; Hematopoiesis; Animal; Hydrolases; Mutation; EC 3.1.3.48; Protein-tyrosine-phosphatase
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v97.4.911

Shp-1 and Shp-2 are cytoplasmic phosphotyrosine phosphatases with similar structures. Mice deficient in Shp-2 die at midgestation with defects in mesodermal patterning, and a hypomorphic mutation at the Shp-1 locus results in the moth-eaten viable (me(v)) phenotype. Previously, a critical role of Shp-2 in mediating erythroid/myeloid cell development was demonstrated. By using the RAG-2-deficient blastocyst complementation, the role of Shp-2 in lymphopoiesis has been determined. Chimeric mice generated by injecting Shp-2(-/-) embryonic stem cells into Rag-2-deficient blastocysts had no detectable mature T and B cells, serum immunoglobulin M, or even Thy-1(+) and B220(+) precursor lymphocytes. Collectively, these results suggest a positive role of Shp-2 in the development of all blood cell lineages, in contrast to the negative effect of Shp-1 in this process. To determine whether Shp-1 and Shp-2 interact in hematopoiesis, Shp-2(-/-):me(v)/me(v) double-mutant embryos were generated and the hematopoietic cell development in the yolk sacs was examined. More hematopoietic stem/progenitor cells were detected in Shp-2(-/-):me(v)/me(v) embryos than in Shp-2(-/-) littermates. The partial rescue by Shp-1 deficiency of the defective hematopoiesis caused by the Shp-2 mutation suggests that Shp-1 and Shp-2 have antagonistic effects in hematopoiesis, possibly through a bidirectional modulation of the same signaling pathway(s).