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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >TRANSGENIC MICE CARRYING THE DIPHTHERIA TOXIN A CHAIN GENE UNDER THE CONTROL OF THE GRANZYME A PROMOTER - EXPECTED DEPLETION OF CYTOTOXIC CELLS AND UNEXPECTED DEPLETION OF CD8 T CELLS
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TRANSGENIC MICE CARRYING THE DIPHTHERIA TOXIN A CHAIN GENE UNDER THE CONTROL OF THE GRANZYME A PROMOTER - EXPECTED DEPLETION OF CYTOTOXIC CELLS AND UNEXPECTED DEPLETION OF CD8 T CELLS

机译：在粒状酶控制下携带白喉毒素链基因的转基因小鼠-预期的细胞毒细胞耗竭和CD8 T细胞的意外耗竭

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We have generated transgenic mice bearing the diphtheria toxin A chain (DTA) gene under the control of granzyme A (GrA) promoter sequences (GrA-DTA). GrA is expressed in activated cytotoxic cells but not in their immediate progenitors, These GrA-DTA mice are deficient in cytotoxic functions, indicating that most cytotoxic cells express GrA in vivo. Surprisingly, one founder strain containing a multicopy GrA-DTA insert show a marked and selective deficiency in CD8(+) cells in peripheral lymphoid organs, This depletion was not observed in thymus, where the distribution of CD4(+) and CD8(+) cells is normal, Moreover, the emigration of T cells from thymus is normal, indicating that the depletion occurs in the periphery. GrA-DTA mice should be useful as models to dissect the role of cytotoxic cells in immune responses and as recipients of normal and neoplastic hematopoietic cells. The selective depletion of CD8(+) cells in one founder strain could have implications for postthymic T-cell development. [References: 39]
机译：我们已经产生了在粒酶A（GrA）启动子序列（GrA-DTA）的控制下携带白喉毒素A链（DTA）基因的转基因小鼠。 GrA在活化的细胞毒性细胞中表达，但不在其直接祖细胞中表达。这些GrA-DTA小鼠的细胞毒性功能不足，表明大多数细胞毒性细胞都在体内表达GrA。令人惊讶的是，一个包含多份GrA-DTA插入片段的创始菌株在外周淋巴器官的CD8（+）细胞中显示出明显的选择性缺陷，在胸腺中未观察到这种耗竭，那里的CD4（+）和CD8（+）分布此外，T细胞从胸腺的迁移是正常的，这表明耗尽发生在外周。 GrA-DTA小鼠应作为解剖细胞毒性细胞在免疫反应中的作用的模型，以及作为正常和赘生性造血细胞的接受者。在一个创始菌株中的CD8（+）细胞的选择性消耗可能对胸腺后T细胞发育有影响。 [参考：39]

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