Pan Lihua, Hanrahan Jenifer, Li Jie, Hale Laura P, Zhuang Yuan
Department of Immunology and Pathology, Duke University Medical Center, Durham, NC 27710, USA.
J Immunol. 2002 Apr 15;168(8):3923-32. doi: 10.4049/jimmunol.168.8.3923.
The importance of E2A transcription factors in T cell development has been demonstrated in studies of E2A-deficient mice, which display abnormal T cell development and a high frequency of T cell lymphomas. Because E2A expression is not restricted to the T cell lineage, the primary cause of the T cell phenotype in E2A-deficient mice was not fully determined. To further investigate the role of E2A in T cell lineage, we generated mice with the E2A gene disrupted exclusively during thymocyte development using the Cre-lox system. We show that this system allows E2A gene disruption to occur throughout the double-negative stage of thymocyte development. E2A deletion appears to be completed before development reaches the double-positive stage. Consistent with the gene disruption, these mice reveal a T cell intrinsic role for E2A during the transition from the double-negative stage to the double-positive stage of thymocyte development. In contrast to germline E2A knockout mice, conditional E2A knockout mice do not develop T cell lymphoma. This work establishes a new model for further investigating E2A function in T cell development and leukemiogenesis.
E2A转录因子在T细胞发育中的重要性已在E2A缺陷小鼠的研究中得到证实，这些小鼠表现出异常的T细胞发育和高频率的T细胞淋巴瘤。由于E2A的表达并不局限于T细胞谱系，E2A缺陷小鼠中T细胞表型的主要原因尚未完全确定。为了进一步研究E2A在T细胞谱系中的作用，我们使用Cre-lox系统构建了在胸腺细胞发育过程中仅E2A基因被破坏的小鼠。我们表明，该系统允许E2A基因在胸腺细胞发育的整个双阴性阶段发生破坏。E2A的缺失似乎在发育达到双阳性阶段之前就已完成。与基因破坏一致，这些小鼠揭示了E2A在胸腺细胞发育从双阴性阶段向双阳性阶段转变过程中的T细胞内在作用。与种系E2A敲除小鼠不同，条件性E2A敲除小鼠不会发生T细胞淋巴瘤。这项工作建立了一个新模型，用于进一步研究E2A在T细胞发育和白血病发生中的功能。
