Loss of adenomatous polyposis coli gene function disrupts thymic development

Nat Immunol. 2005 Aug;6(8):800-9. doi: 10.1038/ni1228. Epub 2005 Jul 17.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


  • Adenomatous Polyposis Coli Protein
  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • Membrane Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Notch
  • Trans-Activators
  • beta Catenin
  • VDJ Recombinases