Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76
Impaired viability and profound block in thymocyte development in mice lacking the adaptor protein SLP-76
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DOI：
10.1016/s0092-8674(00)81422-1
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发表时间：
1998-07-24
期刊：
影响因子：
64.5
通讯作者：
Geha, RS
中科院分区：
文献类型：
--
作者：
Pivniouk, V;Tsitsikov, E;Geha, RS
衔接蛋白SLP-76在T淋巴细胞和髓细胞中表达，是ZAP-70和Syk的底物。我们在小鼠胚胎干细胞中通过同源重组产生了SLP-76零突变，以评估SLP-76在T细胞发育和激活中的作用。slp -76缺陷小鼠表现出皮下和腹腔出血和生存能力受损。淋巴样细胞分析显示胸腺发育严重受阻，缺少双阳性CD4(+)8（+）胸腺细胞和外周T细胞。这种阻滞不能通过抗cd3在体内治疗来克服。TCR β位点的V-D-J重排不受明显影响。B细胞发育正常。这些结果表明SLP-76收集了所有驱动双阳性胸腺细胞发育和扩增的前tcr信号。
The adaptor protein SLP-76 is expressed in T lymphocytes and myeloid cells and is a substrate for ZAP-70 and Syk. We generated a SLP-76 null mutation in mice by homologous recombination in embryonic stem cells to evaluate the role of SLP-76 in T cell development and activation. SLP-76-deficient mice exhibited subcutaneous and intraperitoneal hemorrhaging and impaired viability. Analysis of lymphoid cells revealed a profound block in thymic development with absence of double-positive CD4(+)8(+) thymocytes and of peripheral T cells. This block could not be overcome by in vivo treatment with anti-CD3. V-D-J rearrangement of the TCR beta locus was not obviously affected. B cell development was normal. These results indicate that SLP-76 collects all pre-TCR signals that drive the development and expansion of double-positive thymocytes.