Developmental defects of lymphoid cells in Jak3 kinase-deficient mice
Developmental defects of lymphoid cells in Jak3 kinase-deficient mice
复制标题
DOI：
10.1016/1074-7613(95)90066-7
复制
发表时间：
1995-12-01
期刊：
影响因子：
32.4
通讯作者：
Saito, T
中科院分区：
文献类型：
--
作者：
Park, SY;Saijo, K;Saito, T
Jak 3是一种酪氨酸激酶，其通过与细胞因子受体如IL-2、IL-4、IL-7、IL-9和IL-15的共同γ链缔合来介导细胞因子受体信号传导。与Jak家族的其他成员不同，Jak 3的表达在造血细胞中受到高度限制。为了阐明Jak 3的体内功能，通过同源重组产生Jak 3缺陷型小鼠。Jak 3无效突变的纯合子小鼠表现出严重的缺陷，特别是在淋巴细胞中。骨髓中的B细胞前体、胸腺细胞以及脾脏中的T细胞和B细胞急剧减少，尽管这些缺陷随着年龄的增长而显著恢复。外周淋巴结、NK细胞、树突状表皮T细胞和肠上皮内γ δ T细胞均不存在。来自Jak 3缺陷小鼠的骨髓中的造血干细胞的正常数量和与野生型小鼠类似的产生骨髓和红细胞集落的能力表明淋巴干细胞的特异性缺陷。此外，淋巴器官的异常结构表明Jak 3参与上皮细胞的功能。在突变小鼠中发育的T细胞对IL-2、IL-4或IL-7都没有反应。这些发现确立了Jak 3在淋巴细胞发育中的关键作用。
Jak3 is a tyrosine kinase mediating cytokine receptor signaling through the association with the common gamma chain of the cytokine receptors such as IL-2, IL-4, IL-7, IL-9, and IL-15. Unlike other members of the Jak family, the expression of Jak3 is highly restricted in hematopoietic cells. To elucidate in vivo function of Jak3, Jak3-deficient mice were generated by homologous recombination. Mice homozygous for Jak3 null mutation showed severe defects, specifically in lymphoid cells. B cell precursors in bone marrow, thymocytes, and both T and B cells in the spleen drastically decreased, although these defects were significantly recovered as aging occurred. Peripheral lymph nodes, NK cells, dendritic epidermal T cells, and intestinal intraepithelial gamma delta T cells were absent. Normal number of hematopoietic stem cells in bone marrow from Jak3-deficient mice and the similar capability to generate myeloid and erythroid colonies as wild-type mice indicated specific defects in lymphoid stem cells. Furthermore, the abnormal architecture of lymphoid organs suggested the involvement of Jak3 in the function of epithelial cells. T cells developed in the mutant mice did not respond to either IL-2, IL-4, or IL-7. These findings establish the crucial role of Jak3 in the development of lymphoid cells.