CLONING, DEVELOPMENTAL EXPRESSION, AND EVIDENCE FOR ALTERNATIVE SPLICING OF THE MURINE TUBEROUS SCLEROSIS (TSC2) GENE-PRODUCT

Tuberous sclerosis (TS) is a genetically heterogeneous disease charact erized by the widespread appearance of nonmalignant growths that affec t multiple organ systems. A TS disease-determining gene, located at 16 p13.3 and designated TSC2, has recently been cloned. In this report, t he murine TSC2 homologue was cloned and characterized. cDNA clones enc ompassing the entire murine TSC2 transcript were isolated. Sequence an alysis revealed a high degree of homology between the deduced amino ac id sequence of the murine and human gene products. Northern blot surve ys demonstrated widespread TSC2 expression which was subject to develo pmental regulation in a tissue-specific manner. Although high levels o f TSC2 transcripts were observed in many adult tissues, protein analys es are required to determine whether functional tuberin protein is syn thesized. Reverse transcription-polymerase chain reaction analyses ide ntified at least six regions of alternative splicing, several of which modified putative regulatory motifs in the deduced amino acid structu re of the TSC2 protein.