J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/08/683/11 $2.00
Volume 186, Number 5, August 29, 1997 683-693

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

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

From the ^* Department of Biochemistry,  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.

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