| First Author | Gounari F | Year | 2005 |
| Journal | Nat Immunol | Volume | 6 |
| Issue | 8 | Pages | 800-9 |
| PubMed ID | 16025118 | Mgi Jnum | J:100461 |
| Mgi Id | MGI:3588595 | Doi | 10.1038/ni1228 |
| Citation | Gounari F, et al. (2005) Loss of adenomatous polyposis coli gene function disrupts thymic development. Nat Immunol 6(8):800-9 |
| abstractText | 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. |
