Impaired bone marrow microenvironment and immune function in T cell protein tyrosine phosphatase-deficient mice.
Impaired bone marrow microenvironment and immune function in T cell protein tyrosine phosphatase-deficient mice.
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DOI：
10.1084/jem.186.5.683
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发表时间：
1997-08-29
影响因子：
15.3
通讯作者：
Tremblay, M L
中科院分区：
文献类型：
--
作者：
You-Ten, K E;Muise, E S;Itie, A;Michaliszyn, E;Wagner, J;Jothy, S;Lapp, W S;Tremblay, M L
T细胞蛋白酪氨酸磷酸酶（TC-PTP）是哺乳动物造血细胞中最丰富的酪氨酸磷酸酶之一；然而，其在造血细胞功能中的作用尚不清楚。在本报告中，我们通过生成TC-PTP缺陷突变小鼠来研究TC-PTP的生理功能。三种基因型（+/+,+/−,- /−）在出生时显示孟德尔分离（1:2:1），表明TC-PTP缺失在子宫内不会致死，但所有纯合突变小鼠在3-5周龄时死亡，表现为瘦弱，脾肿大和淋巴结病。纯合子小鼠表现出骨髓（BM）、B细胞淋巴生成和红细胞生成的特异性缺陷，以及T细胞和B细胞功能受损。然而，骨髓和巨噬细胞的发育以及胸腺的T细胞的发育没有明显的影响。骨髓移植实验表明，TC-PTP−/−动物的造血功能衰竭不是由于干细胞缺陷，而是由于基质细胞缺乏。本研究表明TC-PTP在造血和免疫功能中都有重要作用。
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.