The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/8/683/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 5, August 29, 1997 683-693

Article

Impaired Bone Marrow Microenvironment and Immune Function in T Cell Protein Tyrosine Phosphatase–deficient Mice

Kong E. You-Ten*, Eric S. Muise*, Annick Itié*, Eva Michaliszyn*, John Wagner*, Serge Jothy{ddagger}, Wayne S. Lapp§, and Michel L. Tremblay*

From the * Department of Biochemistry, {ddagger} Department of Pathology, and § Department of Physiology, McGill University, Montreal, Quebec, Canada H3G 1Y6

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.

Address correspondence to Michel L. Tremblay, Department of Biochemistry, McGill University, 3655 Drummond St., Rm 904, McIntyre Medical Sciences Building, Montreal, Quebec, Canada H3G 1Y6. Phone: 514-398-7290; FAX: 514-398-7384; E-mail: tremblay{at}medcor.mcgill.ca

E.S. Muise received studentships from the Canderel Foundation and the Fonds pour la formation de Chercheurs et l'Aide à la Recherche, and M.L. Tremblay is a Chercheur-Boursier from the Fonds de la Recherche en Santé du Québec. This work was supported by a Terry Fox research grant to M.L. Tremblay from the National Cancer Institute of Canada and by operating grants from the Cancer Research Society and from the Medical Research Council of Canada grant No. MT12466 to M.L. Tremblay, MT10315 to S. Jothy, and MT3526 to W.S. Lapp.

1 Abbreviations used in this paper: aa, amino acid; BM, bone marrow; ES, embryonic stem; nc, nucleotide; neo, neomycin; PFC, plaque-forming cell; PTP, protein tyrosine phosphatase; PTK, protein tyrosine kinase; SRBC, sheep RBC; TC-PTP, T cell PTP.


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