Abstract
The Eker rat hereditary renal carcinoma (RC) is an excellent example of a mendelian dominant predisposition to a specific cancer in an experimental animal. We have previously established a new conserved linkage group on rat chromosome 10q and human chromosome 16p13.3, and shown that the Eker mutation is tightly linked to the tuberous sclerosis (Tsc2) gene. We now describe a germline mutation in the gene encoding Tsc2 caused by the insertion of an approximately 5 kilobase DNA fragment in the Eker rat, resulting in aberrant RNA expression from the mutant allele. The phenotype of tuberous sclerosis in humans differs from that of the Eker rat, except for the occurence of renal tumours. The Eker rat may therefore provide insights into species–specific differences in tumourigenesis and/or phenotype–specific mutations.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Knudson, A.G. Antloncogenes and human cancer. Proc. natn. Acad. Sci. U.S.A 90, 10914–10921 (1993).
Eker, R. & Mosslge, J.A. A dominant gene for renal adenomas in the rats. Nature 189, 858–859 (1961).
Everitt, J.I., Goldsworthy, T.L., Wolf, D.C. & Walker, C.L. Hereditary renal cell carcinoma In the Eker rat: a rodent familial cancer syndrome. J. Urol. 148, 1932–1936 (1992).
Hino, O. et al. Spontaneous and radiation-induced renal tumours in the Eker rat model of dominantly inherited cancer. Proc. natl. Acad. Sci. U.S.A. 90, 327–331 (1993).
Yeung, R.S., Buetow, K.H., Testa, J.R. & Knudson, A.Q. Susceptibility to renal carcinoma In the Eker rat Involves a tumour suppressor gene on chromosome 10. Proc. natl. Acad. Sci. U.S.A 90, 8038–8042 (1993).
Hino, O., Mltani, H., Nishizawa, M., Katsuyama, H., Kobayashi, E. & Hlrayama, Y. A novel renal cell carcinoma susceptibility gene maps on chromosome 10 in the Eker rat.Jpn. J. Cancer Res. 84, 1106–1109 (1993).
Kubo, Y., Mitani, H. & Hino, O. Allelic loss at the predisposing gene locus in spontaneous and chemically induced renal cell carcinomas in the Eker rat. Cancer Res. 54, 2633–2635 (1994).
Hino, O. et al Universal mapping probes and origin of human chromosome 3. Proc. natl Acad. Sci. U.S.A 90, 730–734 (1993).
Latif, F.L. et al. Identification of the von Hippel-Lindau disease tumour suppressor gene. Science 260, 1317–1320 (1993).
Hino, O., Mitani, H. & Knudson, A.G. Genetic predisposition to transplacentally renal cell carcinomas in the Eker rat. Cancer Res. 53, 5856–6858 (1993).
Hino, O., Mitani, H., Katsuyama, H. & Kubo, Y. A novel cancer predisposition syndrome in the Eker rat model. Cancer Lett. 83, 117–121 (1994).
Hino, O. et al. 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 (1994).
The polycytlc kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16. Cell 77, 881–894 (1994).
Gnarra, J.R. et al. Mutations of the VHL tumour suppressor gene in renal carcinoma. Nature Genet. 7, 85–90 (1994).
Green, A.J., Smith, M. & Yates, J.R.W. Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients. Nature Genet. 6, 193–196 (1994).
Jacks, T., Shin, T.S., Schmitt, E.M., Bronson, R.T., Bernards, A. & Weinberg, R.A. Tumour predisposition in mice heterozygous for a trageted mutation in Nf1. Nature Genet. 7, 353–361 (1994).
Wu, J., Forbes, J.R., Chen, H.S. & Cox, D.W. The LEC rat has a deletion in the copper transporting ATPase gene homologous to the Wilson disease gene. Nature Genet. 7, 541–545 (1994).
Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 75, 1305–1315 (1993).
Hino, O., Kitagawa, T. & Sugano, H. Relationship between serum and hlstochemical markers for hepatitis B virus and rate of viral integration in hepatocellular carcinoma in Japan. Int. J. Cancer 35, 5–10 (1985).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kobayashi, T., Hirayama, Y., Kobayashi, E. et al. 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). https://doi.org/10.1038/ng0195-70
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ng0195-70
This article is cited by
-
Transgenic expression of the N525S-tuberin variant in Tsc2 mutant (Eker) rats causes dominant embryonic lethality
Scientific Reports (2014)
-
13-year-old tuberous sclerosis patient with renal cell carcinoma associated with multiple renal angiomyolipomas developing multifocal micronodular pneumocyte hyperplasia
BMC Clinical Pathology (2013)
-
Genetic control of renal tumorigenesis by the mouse Rtm1 locus
BMC Genomics (2013)
-
Renal cell carcinoma: translational aspects of metabolism and therapeutic consequences
Kidney International (2013)
-
mTORC1 enhancement of STIM1-mediated store-operated Ca2+ entry constrains tuberous sclerosis complex-related tumor development
Oncogene (2013)
