1. ¹Department of Pathology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
2. ²The YS Institute Inc., Utsunomiya, Tochigi, Japan
3. ³Toxicology Group, Safety Research Laboratories, Dainippon Pharmaceutical Co., Ltd, Suita, Osaka, Japan

Correspondence: Dr O Hino, Department of Pathology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail: ohino@med.juntendo.ac.jp

Received 8 July 2005; Revised 18 October 2005; Accepted 6 November 2005; Published online 12 December 2005.

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.