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The Journal of Immunology, 2002, 168: 3923-3932.
Copyright © 2002 by The American Association of Immunologists

An Analysis of T Cell Intrinsic Roles of E2A by Conditional Gene Disruption in the Thymus1

Lihua Pan*, Jenifer Hanrahan*, Jie Li{dagger}, Laura P. Hale{dagger} and Yuan Zhuang2,*

Departments of * Immunology and {dagger} Pathology, Duke University Medical Center, Durham, NC 27710

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.




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