A Novel Renal Carcinoma Predisposing Gene of the Nihon Rat Maps on Chromosome 10

Abstract

A novel rat model of hereditary renal cell carcinoma (RC) was found in a rat colony of the Spra‐gue‐Dawley (SD) strain in Japan, and named the “Nihon” rat in 2000. This study was designed to map the RC susceptibility gene in the Nihon rat using 113 backcross annuals. Our present data clearly show that the Nihon gene is genetically linked to interleukin‐3 (IL3) gene (χ2=93.6, Lod score=25.16), lethal (2) giant larvae (LLGL1) locus (χ2=109.0, Lod score=31.56) and myosin heavy chain, embryonic skeletal muscle (MYHSE) gene (χ2=90.6, Lod score=23.87), which are located on the distal part of rat chromosome 10. The order of the genes is the Eker (Tsc2) gene (located on the proximal part of rat chromosome 10; human chromosome 16p 13.3)–21.3 cM–IL3 gene (human 5q23‐31)–4.4 cM–Nihon gene–0.9 cM–LLGL1 locus (human 17p11.2)‐4.4 cM–MYHSE gene (human 17pl3.1). We also detected loss of the wild‐type allele at the MYHSE locus, fitting Knudson's “two hit” model. Thus, the Nihon rat should have a mutation of a novel tumor suppressor gene related to renal carcinogenesis.