An HMG-box-containing T-cell factor required for thymocyte differentiation

Nature. 1995 Mar 2;374(6517):70-4. doi: 10.1038/374070a0.


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.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Cycle
  • Cell Differentiation
  • DNA
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Germ-Line Mutation
  • Hepatocyte Nuclear Factor 1-alpha
  • Homeodomain Proteins / physiology*
  • Immunophenotyping
  • Lymphocyte Count
  • Lymphoid Enhancer-Binding Factor 1
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • T Cell Transcription Factor 1
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • Thymus Gland / cytology*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*


  • DNA-Binding Proteins
  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, mouse
  • Homeodomain Proteins
  • Lef1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • T Cell Transcription Factor 1
  • Transcription Factors
  • DNA