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Loss of adenomatous polyposis coli gene function disrupts thymic development.

Loss of the adenomatous polyposis coli (APC) protein is a common initiating event in colon cancer. Here we show that thymocyte-specific loss of APC deregulated beta-catenin signaling and suppressed Notch-dependent transcription. These events promoted the proliferation of cells of the double-negative 3 and 4 stages and reduced rearrangements between the variable, diversity and joining regions of the gene encoding T cell receptor (TCR) beta, encouraging developmental progression of aberrant thymocytes lacking pre-TCR and alphabeta TCR. Simultaneously, the loss of APC prolonged the mitotic metaphase-to-anaphase checkpoint and impaired chromosome segregation, blocking development beyond the double-negative 4 stage. The result was extensive thymic atrophy and increased frequencies of thymocytes with chromosomal abnormalities. Thus, loss of APC in immature thymocytes has consequences distinct from those of deregulation of beta-catenin signaling and is essential for T cell differentiation.

Pubmed ID: 16025118


  • Gounari F
  • Chang R
  • Cowan J
  • Guo Z
  • Dose M
  • Gounaris E
  • Khazaie K


Nature immunology

Publication Data

August 21, 2005

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01 AI059676
  • Agency: NIAID NIH HHS, Id: R01 AI059676-01
  • Agency: NIAID NIH HHS, Id: R01 AI059676-02
  • Agency: NCI NIH HHS, Id: R01 CA104547
  • Agency: NCI NIH HHS, Id: R01 CA104547-01A1

Mesh Terms

  • Adenomatous Polyposis Coli Protein
  • Alleles
  • Anaphase
  • Animals
  • Cell Proliferation
  • Cell Survival
  • Cells, Cultured
  • Chromosome Aberrations
  • Chromosome Banding
  • Cytokinesis
  • Cytoskeletal Proteins
  • Flow Cytometry
  • Gene Expression Regulation, Developmental
  • Gene Rearrangement
  • Genes, APC
  • Genotype
  • Membrane Proteins
  • Metaphase
  • Mice
  • Mice, Transgenic
  • Mitosis
  • Models, Genetic
  • Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Notch
  • Recombination, Genetic
  • Retroviridae
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • T-Lymphocytes
  • Thymus Gland
  • Trans-Activators
  • VDJ Recombinases
  • beta Catenin