REGULATED EXPRESSION OF HUMAN CD4 RESCUES HELPER T-CELL DEVELOPMENT IN MICE LACKING EXPRESSION OF ENDOGENOUS CD4
REGULATED EXPRESSION OF HUMAN CD4 RESCUES HELPER T-CELL DEVELOPMENT IN MICE LACKING EXPRESSION OF ENDOGENOUS CD4
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DOI：
10.1002/j.1460-2075.1993.tb05798.x
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发表时间：
1993-04-01
期刊：
影响因子：
11.4
通讯作者：
LITTMAN, DR
中科院分区：
文献类型：
--
作者：
KILLEEN, N;SAWADA, S;LITTMAN, DR
在T细胞发育期间，共同表达CD4和CD8糖蛋白的前体胸腺细胞会产生表达其中一种分子的成熟后代，而不表达另一种分子。仅持续表达CD4是成熟辅助T细胞的标志，而细胞毒性T细胞表达CD8并消灭CD4。产生两个T细胞亚群的分化程序可能与这些细胞表面分子的表达调控密切相关。我们现在描述了使用小鼠的CD4增强子来产生表达生理水平的人类CD4的转基因小鼠。转基因在T细胞发育过程中受到适当的调控，并包括必要的顺式作用序列，以消除CD8谱系中的表达。此外，在内源性CD_4基因失活的小鼠中，转基因人CD_4介导了CD_4谱系的恢复和正常辅助细胞功能的恢复。这些小鼠的产生体现了为人类免疫系统开发可靠的动物模型的一般方法。
During T cell development, precursor thymocytes that co-express the CD4 and CD8 glycoproteins give rise to mature progeny expressing one of these molecules to the exclusion of the other. Continued expression of only CD4 is the hallmark of mature helper T cells, whereas cytotoxic T cells express CD8 and extinguish CD4. The differentiation program that generates the two T cell subsets is likely to be intimately tied to regulation of expression of these cell surface molecules. We now describe the use of a murine CD4 enhancer in the generation of transgenic mice expressing physiologic levels of human CD4. The transgene is appropriately regulated during T cell development and includes the necessary cis-acting sequences for extinguishing expression in the CD8 lineage. Furthermore, in mice whose endogenous CD4 gene is inactivated, the transgenic human CD4 mediates rescue of the CD4 lineage and restoration of normal helper cell functions. The generation of these mice exemplifies a general approach for developing reliable animal models for the human immune system.