| First Author | Berkovich I | Year | 2001 |
| Journal | Diabetes | Volume | 50 |
| Issue | 10 | Pages | 2260-7 |
| PubMed ID | 11574407 | Mgi Jnum | J:71705 |
| Mgi Id | MGI:2150588 | Doi | 10.2337/diabetes.50.10.2260 |
| Citation | Berkovich I, et al. (2001) Inducible and Reversible beta-Cell Autoimmunity and Hyperplasia in Transgenic Mice Expressing a Conditional Oncogene. Diabetes 50(10):2260-7 |
| abstractText | Expression of the SV40 T antigen (Tag) in pancreatic beta-cells in transgenic mice has been shown to induce beta-cell tumorigenesis. We generated transgenic mice in which Tag expression is inducible and reversible by the tet-on gene regulation system. These mice develop beta-cell tumors only when treated with the inducer doxycycline (dox). Tag expression in vivo is reversible upon dox withdrawal. As a result, beta-cell proliferation is greatly reduced, indicating that genetic changes, which may occur in the transformed cells, do not allow Tag-independent proliferation. Induction of Tag expression after immune recognition of self-antigens has been established triggers an autoimmune response against beta-cells, as evidenced by insulitis. Shut-off of Tag expression results in elimination of insulitis, suggesting that this process depends on continuous expression of the target antigen. In addition, the reversibility of autoimmunity suggests that beta-cell damage caused by the anti-Tag immune response does not elicit secondary responses to other newly exposed beta-cell antigens, which would have persisted after Tag elimination. beta-Cell proliferation in this model is accompanied by cell apoptosis. Apoptosis persisted for several weeks in the islets after dox removal. In close to 40% of the mice analyzed, this process reduced the islet size back to normal, suggesting the existence of a homeostatic mechanism that maintains beta-cell mass within the normal range. |
