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Transgenic rescue from embryonic lethality and renal carcinogenesis in the Nihon rat model by introduction of a wild-type Bhd gene

Oncogene volume 25, pages 2885–2889 (2006)Cite this article

Abstract

We recently reported that a germline insertion of a single nucleotide in the rat homologue of the human Birt–Hogg–Dubé gene (BHD) gives rise to dominantly inherited cancer in the Nihon rat model. In this study, we constructed transgenic Nihon rats with introduction of a wild-type Bhd gene to ascertain whether suppression of the Nihon phenotype is possible. Rescue from embryonic lethality of mutant homozygotes (Nihon/Nihon) and suppression of renal carcinogenesis in heterozygotes (Nihon/+) were both observed, defining the germline Bhd mutation in the Nihon rat as an embryonal lethal and tumor predisposing mutation. This transgenic rescue system will be useful to analyse Bhd gene function, its relation to tumorigenesis in vivo, and genetic–environmental interactions in carcinogenesis.

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Acknowledgements

We thank Ri-ichi Takahashi for the generation of transgenic rats, Hiroaki Mitani, Junko Sakurai, Youko Hirayama and Etsuko Kobayashi for technical supports. This work was supported by a Grant-in-Aid for Cancer Research and Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports and Science and Technology of Japan and the Ministry of Health, Labour and Welfare of Japan.

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Authors and Affiliations

  1. Department of Pathology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan

    Y Togashi, T Kobayashi, S Momose & O Hino

  2. The YS Institute Inc., Utsunomiya, Tochigi, Japan

    M Ueda

  3. Toxicology Group, Safety Research Laboratories, Dainippon Pharmaceutical Co., Ltd, Suita, Osaka, Japan

    K Okimoto

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  1. Y Togashi
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  2. T Kobayashi
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  3. S Momose
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  4. M Ueda
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  6. O Hino
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Correspondence to O Hino.

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Togashi, Y., Kobayashi, T., Momose, S. et al. Transgenic rescue from embryonic lethality and renal carcinogenesis in the Nihon rat model by introduction of a wild-type Bhd gene. Oncogene 25, 2885–2889 (2006). https://doi.org/10.1038/sj.onc.1209317

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