title: Natural history of the Nihon rat model of BHD.
abstract: Hereditary cancer was first described in the rat by Eker and Mossige in 1954 in Oslo. The Eker rat model of hereditary renal carcinoma (RC) was the first example of a Mendelian dominantly inherited predisposition to a specific cancer in an experimental animal, and has been contributing to the elucidation of renal carcinogenesis. Recently, we found a second hereditary RC model in the Sprague-Dawley (SD) rat, in Japan in 2000, which was named the Nihon rat. The Nihon rat is also an example of a Mendelian dominantly inherited predisposition for development of RCs like the Eker rat, which are predominantly of the clear cell type (this type represents approximately 75 % of human RCC), and develop from earlier preneoplastic lesions than the Eker rat. We performed a genetic linkage analysis of the Nihon rat using 113 backcross animals, and found that the Nihon mutation was tightly linked to genes, which are located on the distal part of rat chromosome 10. Finally, we identified a germline mutation in the Birt-Hogg-Dubé gene (Bhd) (rat chromosome 10, human chromosome 17p11.2) caused by the insertion of a single nucleotide in the Nihon rat gene sequence, resulting in a frame shift and producing a stop codon 26 amino acids downstream. Thus, the Nihon rat will contribute to understanding the BHD gene function and renal carcinogenesis.
authors.affiliation: Toxicology Group, Safety Research Laboratories, Dainippon Pharmaceutical Co., Ltd., 33-94 Enoki-cho., Suita, Osaka 564-0053, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Okimoto
authors.forename: Mami
authors.initials: M
authors.lastname: Kouchi
authors.forename: Izumi
authors.initials: I
authors.lastname: Matsumoto
authors.forename: Junko
authors.initials: J
authors.lastname: Sakurai
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Okio
authors.initials: O
authors.lastname: Hino
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D006720:Homozygote; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D011506:Proteins / Q000235:genetics*; D051381:Rats; D011922:Rats, Mutant Strains
chemical_list: C482582:Flcn protein, rat; D011506:Proteins