Cloning, developmental expression, and evidence for alternative splicing of the murine tuberous sclerosis (TSC2) gene...

Tuberous sclerosis (TS) is a genetically heterogeneous disease characterized by the widespread appearance of nonmalignant growths that affect multiple organ systems. A TS disease-determining gene, located at 16p13.3 and designated TSC2, has recently been cloned. In this report, the murine TSC2 homologue was cloned and characterized. cDNA clones encompassing the entire murine TSC2 transcript were isolated. Sequence analysis revealed a high degree of homology between the deduced amino acid sequence of the murine and human gene products. Northern blot surveys demonstrated widespread TSC2 expression which was subject to developmental regulation in a tissue-specific manner. Although high levels of TSC2 transcripts were observed in many adult tissues, protein analyses are required to determine whether functional tuberin protein is synthesized. Reverse transcription-polymerase chain reaction analyses identified at least six regions of alternative splicing, several of which modified putative regulatory motifs in the deduced amino acid structure of the TSC2 protein.