| First Author | Kobayashi T | Year | 1999 |
| Journal | Cancer Res | Volume | 59 |
| Issue | 6 | Pages | 1206-11 |
| PubMed ID | 10096549 | Mgi Jnum | J:52464 |
| Mgi Id | MGI:1333508 | Citation | Kobayashi T, et al. (1999) Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by a germ-line Tsc2 mutation in mice. Cancer Res 59(6):1206-11 |
| abstractText | Germ-line mutations of the human TSC2 tumor suppressor gene cause tuberous sclerosis (TSC), a disease characterized by the development of hamartomas in various organs. In the Eker rat, however, a germ-line Tsc2 mutation gives rise to renal cell carcinomas with a complete penetrance The molecular mechanism for this phenotypic difference between man and rat is currently unknown, and the physiological function of the TSC2/Tsc2 product (tuberin) is not fully understood. To investigate these unsolved problems, we have generated a Tsc2 mutant mouse Tsc2 heterozygous mutant (Tsc+/-) mice developed renal carcinomas with a complete penetrance, as seen in the Eker rat, but not the angiomyolipomas characteristic of human TSC, confirming the existence of a species- specific mechanism of tumorigenesis caused by tuberin deficiency. Unexpectedly, similar to 80% of Tsc2+/- mice also developed hepatic hemangiomas that are not observed in either TSC or the Eker rat, Tsc2 homozygous (Tsc2-/-) mutants died around embryonic day 10.5, indicating an essential function for tuberin in mouse embryonic development. Some Tsc2-/- embryos exhibited an unclosed neural tube and/or thickened myocardium. The latter is associated with increased cell density that may be a reflection of loss of a growth-suppressive function of tuberin. The mouse strain described here should provide a valuable experimental model to analyze the function of tuberin and its association with tumorigenesis. |
