An HMG-box-containing T-cell factor required for thymocyte differentiation.
Two candidate genes for controlling thymocyte differentiation, T-cell factor-1 (Tcf-1) and lymphoid enhancer-binding factor (Lef-1), encode closely related DNA-binding HMG-box proteins. Their expression pattern is complex and largely overlapping during embryogenesis, yet restricted to lymphocytes postnatally. Here we generate two independent germline mutations in Tcf-1 and find that thymocyte development in (otherwise normal) mutant mice is blocked at the transition from the CD8+, immature single-positive to the CD4+/CD8+ double-positive stage. In contrast to wild-type mice, most of the immature single-positive cells in the mutants are not in the cell cycle and the number of immunocompetent T cells in peripheral lymphoid organs is reduced. We conclude that Tcf-1 controls an essential step in thymocyte differentiation.
Verbeek
S
S
Department of Immunology, University Hospital, Utrecht, The Netherlands.
Izon
D
D
Hofhuis
F
F
Robanus-Maandag
E
E
te Riele
H
H
van de Wetering
M
M
Oosterwegel
M
M
Wilson
A
A
MacDonald
H R
HR
Clevers
H
H
D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle; D002454:Cell Differentiation; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018095:Germ-Line Mutation; D051538:Hepatocyte Nuclear Factor 1-alpha; D018398:Homeodomain Proteins / Q000502:physiology*; D016130:Immunophenotyping; D018655:Lymphocyte Count; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D051822:T Cell Transcription Factor 1; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D018398:Homeodomain Proteins; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D051822:T Cell Transcription Factor 1; D014157:Transcription Factors; D004247:DNA