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

KE You-Ten, ES Muise, A Itié, E Michaliszyn… - The Journal of …, 1997 - rupress.org
KE You-Ten, ES Muise, A Itié, E Michaliszyn, J Wagner, S Jothy, WS Lapp, ML Tremblay
The Journal of experimental medicine, 1997rupress.org
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 …
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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