CDNA STRUCTURE, ALTERNATIVE SPLICING AND EXON-INTRON ORGANIZATION OF THE PREDISPOSING TUBEROUS SCLEROSIS (TSC2) GENE OF THE EKER RAT MODEL

The Eker rat hereditary renal carcinoma (RC) is an excellent example o f a Mendelian dominant predisposition to a specific cancer in an exper imental animal. We recently reported that a germline insertion in the rat homologue of the human tuberous sclerosis gene (TSC2) gives rise t o the dominantly inherited cancer in the Eker rat model. We now descri be the entire cDNA (5375 bp without exons 25 and 31) and genomic struc ture of the rat Tsc2 gene. The deduced amino acid sequence (1743 amino acids) shows 92% identity to the human counterpart. Surprisingly, the re are a great many (greater than or equal to 41) coding exons with sm all sized introns spanning only similar to 35 kb of genomic DNA. Two a lternative splicing events [involving exons 25 (129 bp) and 31 (69 bp) ] make for a complex diversity of the Tsc2 product. The present determ ination of the Tsc2 gene and establishment of strong conservation betw een the rat and man provide clues for assessing unknown gene functions apart from that already predicted from the GTPase activating proteins (GAPS) homologous domain and for future analysis of intragenic mutati ons in tumors using methods such as PCR-SSCP and for insights into div erse phenotypes between species.