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Nucleic Acids Research, 1995, Vol. 23, No. 14 2608-2613
© 1995

MOLECULAR BIOLOGY

cDNA structure, alternative splicing and exon—intron organization of the predisposing tuberous scelerosis (Tsc2) gene of the Eker rat model

Toshiyuki Kobayashi, Masae Nishizawa, Youko Hirayama, Etsuko Kobayashi and Okio Hino*

Department of Experimental Pathology, Cancer Institute 1–37–1 Kami-ikebukuro, Toshima-ku, Tokyo 170, Japan

*To whom correspondence should be addressed

Received May 3, 1995. Accepted June 12, 1995.

The Eker rat hereditary renal carcinoma (RC) is an excellent example of a Mendellan dominant predisposition to a specific cancer in an experimental animal. We recently reported that a germline insertion In the rat homologue of the human tuberous sclerosis gene (TSC2) gives rise to the dominantly inherited cancer in the Eker rat model. We now describe the entire cDNA (5375 bp without exons 25 and 31) and genomlc structure of the rat Tsc2 gene. The deduced amlno acid sequence (1743 amino acids) shows 92% identity to the human counterpart Surprisingly, there are a great many (>41) coding exons with small sized Introns spanning only –35 kb of genomlc DNA. Two alternative splicing events [involving exons 25 (129 bp) and 31 (69 bp)] make for a complex diversity of the Tsc2 product. The present determination of the Tsc2 gene and establishment of strong conservation between the rat and man provide clues for assessing unknown gene functions apart from that already predicted from the GTPase activating proteins (GAP3) homologous domain and for future analysis of intragenic mutations in tumors using methods such as PCR-SSCP and for insights into diverse phenotypes between species.


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