Isolation and characterization of a rat homologue of the human tuberous sclerosis 1 gene (Tsc1) and analysis of its mutations in rat renal carcinomas

In the Eker rat, a germ-line mutation in the homologue of the human tuberou s sclerosis gene (Tsc2) causes renal cell carcinomas (RCs) with a complete penetrance in all heterozygotes, Tsc2 mutations have also been found in a s ubset of chemically induced non-Eker rat RCs, Because tuberous sclerosis pa tients with alteration of either of the two predisposing genes (TSC1 and TS C2) show identical symptoms, the products of these two genes are thought to be involved in a common biological pathway. In this study, to analyze the possible overlap between the functions of Tsc2 and Tsc1 gene products, we i solated and characterized a rat homologue of the TSC1 gene (Tsc1), The rat Tsc1 gene, which has an identical exon-intron structure to that of human TS C1 and is localized on rat chromosome 3, has been shown to encode a protein (hamartin) that is highly homologous to the human counterpart with an simi lar to 86% amino acid sequence identity. Using PCR-single-strand conformati onal polymorphism analysis, we identified two splicing donor site mutations in one chemically induced rat RC (1 of 15). This suggests that alterations of the Tsc1 gene may be involved in the development of a subset of rat RCs .