An analysis of T cell intrinsic roles of E2A by conditional gene disruption in the thymus.
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.
Pan
Lihua
L
Department of Immunology and Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Hanrahan
Jenifer
J
Li
Jie
J
Hale
Laura P
LP
Zhuang
Yuan
Y
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D005786:Gene Expression Regulation / Q000276:immunology; D020868:Gene Silencing / Q000276:immunology; D018390:Gene Targeting / Q000379:methods*; D018257:Helix-Loop-Helix Motifs / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D014157:Transcription Factors; C407909:TCF3 protein, human; C489532:Tcf12 protein, mouse; C073366:TCF12 protein, human