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PMID: 9271584 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Impaired bone marrow microenvironment and immune function in T cell protein tyrosine phosphatase-deficient mice.

The Journal of experimental medicine ·Vol. 186 ·No. 5 ·1997-08-29 ·Pages 683-93

You-Ten KE, Muise ES, Itié A, Michaliszyn E, Wagner J, Jothy S, Lapp WS, Tremblay ML

Abstract

The T cell protein tyrosine phosphatase (TC-PTP) is one of the most abundant mammalian tyrosine phosphatases in hematopoietic cells; however, its role in hematopoietic cell function remains unknown. In this report, we investigated the physiological function(s) of TC-PTP by generating TC-PTP-deficient mutant mice. The three genotypes (+/+, +/-, -/-) showed mendelian segregation at birth (1:2:1) demonstrating that the absence of TC-PTP was not lethal in utero, but all homozygous mutant mice died by 3-5 wk of age, displaying runting, splenomegaly, and lymphadenopathy. Homozygous mice exhibited specific defects in bone marrow (BM), B cell lymphopoiesis, and erythropoiesis, as well as impaired T and B cell functions. However, myeloid and macrophage development in the BM and T cell development in the thymus were not significantly affected. BM transplantation experiments showed that hematopoietic failure in TC-PTP -/- animals was not due to a stem cell defect, but rather to a stromal cell deficiency. This study demonstrates that TC-PTP plays a significant role in both hematopoiesis and immune function.

MeSH Terms
Animals Antigens, CD/analysis B-Lymphocytes/cytology,immunology Bone Marrow/immunology,physiology Bone Marrow Cells Bone Marrow Transplantation Cell Division Gamma Rays Gene Targeting Hematopoiesis Hematopoietic Stem Cells/cytology Homozygote Lymph Nodes/immunology Mice Mice, Inbred BALB C Mice, Knockout Protein Tyrosine Phosphatase, Non-Receptor Type 2 Protein Tyrosine Phosphatases/deficiency,genetics,physiology Spleen/immunology Stromal Cells/cytology,physiology T-Lymphocytes/cytology,enzymology,immunology Thymus Gland/immunology Whole-Body Irradiation
Chemicals
Antigens, CD Protein Tyrosine Phosphatase, Non-Receptor Type 2 Protein Tyrosine Phosphatases Ptpn2 protein, mouse
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
You-Ten K E
Department of Biochemistry, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Muise E S
Itié A
Michaliszyn E
Wagner J
Jothy S
Lapp W S
Tremblay M L
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.186.5.683
Published
1997-08-29
Pages
683-93
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2199020
Subset
IM
Grants
PHS HHS · MT10315 · United States
PHS HHS · MT12466 · United States
PHS HHS · MT3526 · United States
External Links
PubMed source DOI: 10.1084/jem.186.5.683 PMC Full Text View journal details
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