An analysis of T cell intrinsic roles of E2A by conditional gene disruption in the thymus

L Pan, J Hanrahan, J Li, LP Hale… - The Journal of …, 2002 - journals.aai.org
L Pan, J Hanrahan, J Li, LP Hale, Y Zhuang
The Journal of Immunology, 2002journals.aai.org
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 …
Abstract
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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