IMPAIRED BONE-MARROW MICROENVIRONMENT AND IMMUNE FUNCTION IN T-CELL PROTEIN-TYROSINE PHOSPHATASE-DEFICIENT MICE

The T cell protein tyrosine phosphatase (TC-PTP) is one of the most ab undant mammalian tyrosine phosphatases in hematopoietic cells; however , its role in hematopoietic cell function remains unknown. In this rep ort, we investigated the physiological function(s) of TC-PTP by genera ting 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 le thal in utero, but all homozygous mutant mice died by 3-5 wk of age, displaying runting, splenomegaly, and lymp hadenopathy. 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 aff ected. BM transplantation experiments showed that hematopoietic failur e 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 play s a significant role in both he matopoiesis and immune function.