A germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer

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 occurrence of renal tumours. The Eker rat may therefore provide insights into species-specific differences in tumourigenesis and/or phenotype-specific mutations.