Overexpression of the Helix-Loop-Helix protein Id2 blocks T cell development at multiple stages.
The Id proteins are inhibitors of basic-Helix-Loop-Helix transcription factor function that have been implicated in the control of cell differentiation and proliferation. To study the role of Id proteins in the control of T cell development, we generated transgenic mice that overexpress the Id2 protein in thymocytes. We detect a significant expansion of the early CD4(-)CD8(+)TCR(-) thymocyte stage and a depletion of the thymocytes of the subsequent developmental stages. These data indicate that the overexpression of Id2 leads to a stage-specific developmental block early in thymopoiesis. In addition, progeny mice from five of the six Id2 transgenic founder lines succumb to aggressive T cell hyperproliferation that resembles lymphoma. Thus, overexpression of the Id2 protein has profound effects on T cell development and oncogenesis, consistent with the hypothesis that the bHLH proteins play critical roles in these processes.
Morrow
M A
MA
Department of Biology, State University of New York, New Paltz 12561-2499, USA. morrowm@matrix.newpaltz.edu
Mayer
E W
EW
Perez
C A
CA
Adlam
M
M
Siu
G
G
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology*; D005260:Female; D018257:Helix-Loop-Helix Motifs / Q000235:genetics / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D051797:Inhibitor of Differentiation Protein 2; D008213:Lymphocyte Activation / Q000235:genetics; D016399:Lymphoma, T-Cell / Q000209:etiology / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D012097:Repressor Proteins / Q000235:genetics* / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D012097:Repressor Proteins; D014157:Transcription Factors