PMID:16025118

Citation	Gounari, F, Chang, R, Cowan, J, Guo, Z, Dose, M, Gounaris, E and Khazaie, K (2005) Loss of adenomatous polyposis coli gene function disrupts thymic development. Nat. Immunol. 6:800-9
Abstract	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.
Links	PubMed Online version:10.1038/ni1228
Keywords	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
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