Requirement of Shp-2 tyrosine phosphatase in lymphoid and hematopoietic cell development.
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).
Qu
C K
CK
Burnham Institute, La Jolla, CA, USA.
Nguyen
S
S
Chen
J
J
Feng
G S
GS
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D019070:Cell Lineage; D002678:Chimera; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D005314:Embryonic and Fetal Development / Q000235:genetics; D005260:Female; D005816:Genetic Complementation Test; D005838:Genotype; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008214:Lymphocytes / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000166:cytology; D015017:Yolk Sac / Q000166:cytology
D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2