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| Renal carcinogenesis, hepatic hemangiomatosis, and embryonic lethality caused by a germ-line Tsc2 mutation in mice |
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| Author(s): Kobayashi T, Minowa O, Kuno J, Mitani K, Hino O, Noda T |
| Source: CANCER RESEARCH Volume: 59 Issue: 6 Pages: 1206-1211 Published: MAR 15 1999 |
| Times Cited: 121 References: 38 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Hino, O (reprint author), Inst Canc, Dept Expt Pathol, Toshima Ku, 1-37-1 Kami Ikebukuro, Tokyo 1708455, Japan |
Addresses:
1. Inst Canc, Dept Expt Pathol, Toshima Ku, Tokyo 1708455, Japan
2. Inst Canc, Dept Cell Biol, Toshima Ku, Tokyo 1708455, Japan
3. Tohoku Univ, Sch Med, Dept Mol Genet, Sendai, Miyagi 9808575 Japan
4. Japan Sci & Technol Corp, CREST, Kawaguchi 3320012, Japan |
| Publisher: AMER ASSOC CANCER RESEARCH, PO BOX 11806, BIRMINGHAM, AL 35202 USA |
| Subject Category: Oncology |
| IDS Number: 175ZD |
| ISSN: 0008-5472 |
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