Abstract
A novel rat model of hereditary renal cell carcinoma (RC) was found in a rat colony of the Sprague‐Dawley strain in Japan, and named the “Nihon'’rat. In this strain, RCs develop from early preneoplastic lesions, which begin to appear at 4 weeks of age, forming adenomas by the age of 16 weeks. The RCs are predominantly of clear cell type. Southern blot, northern blot and SSCP analyses revealed no change in the Tsc1, Tsc2, VHL, and c‐Met genes. Thus, the Nihon rat should be a valuable experimental model for understanding renal carcinogenesis, especially clear cell type, which is common among human RCs.
Keywords: Nihon rats, Tsc2 gene mutant (Eker) rats, Renal carcinogenesis, Hereditary cancer
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REFERENCES
- 1. ) Eker , R. and Mossige , J.A dominant gene for renal adenomas in the rat . Nature , 189 , 858 – 859 ( 1961. ). 13780066 [Google Scholar]
- 2. ) Hino , O. , Mitani , H. , Nishizawa , M. , Katsuyama , H. , Kobayashi , E. and Hirayama , Y.A novel renal cell carcinoma susceptibility gene maps on chromosome 10 in the Eker rat . Jpn. J. Cancer Res. , 84 , 1106 – 1109 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. ) Hino , O. , Kobayashi , T. , Tsuchiya , H. , Kikuchi , Y. , Kobayashi , E. , Mitani , H. and Hirayama , Y.The predisposing gene of the Eker rat inherited cancer syndrome is tightly linked to the tuberous sclerosis (TSC2) gene . Biochem. Biophys. Res. Commun. , 203 , 1302 – 1308 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Kobayashi , T. , Hirayama , Y. , Kobayashi , E. , Kubo , Y. and Hino , O.A germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer . Nat. Genet. , 9 , 70 – 74 ( 1995. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Kabayashi , T. , Urakami , S. , Hirayama , Y. , Yamamoto , T. , Nishizawa , M. , Takahara T. , Kubo , Y. and Hino , O.Intragenic Tsc2 somatic mutations as Knudson's second hit in spontaneous and chemically induced renal carcinomas in the Eker rat model . Jpn. J. Cancer Res. , 88 , 254 – 261 ( 1997. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. ) Urakami , S. , Tokuzen , R. , Tsuda , H. , Igawa , M. and Hino , O.Somatic mutation of the tuberous sclerosis (Tsc2) tumor suppressor gene in chemically induced rat renal carcinoma cell . J. Urol. , 158 , 275 – 278 ( 1997. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Satake , N. , Urakami , S. , Hirayama , Y. , Izumi , K. and Hino , O.Biallelic mutations of the Tsc2 gene in chemically induced rat renal cell carcinoma . Int. J. Cancer , 77 , 895 – 900 ( 1998. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Satake , N. , Kobayashi , T. , Kobayashi , E. , Izumi , K. and Hino , O.Isolation and characterization of a rat homologue of the human tuberous sclerosis 1 gene (Tsc1) and analysis of its mutations in rat renal carcinomas . Cancer Res. , 59 , 849 – 855 ( 1999. ). [PubMed] [Google Scholar]
- 9. ) Kikuchi , Y. , Kobayashi , E. , Nishizawa , M. , Hamazaki , S. , Okada , S. and Hino , O.Cloning of the rat homologue of the von Hippel‐Lindau tumor suppressor gene and its non‐somatic mutation in rat renal cell carcinomas . Jpn. J. Cancer Res. , 86 , 905 – 909 ( 1995. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. ) Everitt , J. I. , Goldsworthy , T. L. , Wolf , D. C. and Walker , C. L.Hereditary renal cell carcinoma in the Eker rat: a rodent familial cancer syndrome . J. Urol. , 148 , 1932 – 1936 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Hino , O. , Fukuda , T. , Satake , N. , Kobayashi , T. , Honda , S. , Orimoto , K. , Yamashita , Y. and Kikuchi , Y.Tsc2 gene mutant (Eker) rat model of a Mendelian dominantly inherited cancer . Prog. Exp. Tumor Res. , 35 , 95 – 108 ( 1999. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Bannasch , P. and Zerban , H.Animal models and renal carcinogenesis . In “ Tumors and Tumor‐like Conditions of the Kidneys and Ureters ,” ed. Eble J. N. , pp. 1 – 34 ( 1990. ). Livingstone; , New York . [Google Scholar]