STRUCTURE OF THE MOUSE KLOTHO GENE AND ITS 2 TRANSCRIPTS ENCODING MEMBRANE AND SECRETED PROTEIN

We previously established a novel mouse model for human aging and iden tified the genetic foundation responsible for it. A defect in expressi on of a novel gene, termed klotho (kl), leads to a syndrome resembling human aging in mice. The kl gene encodes a single-pass membrane prote in whose extracellular domain carries homology to beta-glucosidases. I n this report, we present the entire mouse kl gene organization. The m ouse kl gene spans about 50 kilobases and consists of five exons. The promoter region lacks a TATA-box and contains four potential binding s ites for SP1. We further show that two kl gene transcripts encoding me mbrane or secreted protein are generated through alternative transcrip tional termination. These findings provide fundamental information for further study of the kl gene which may regulate aging in Five. (C) 19 98 Federation of European Biochemical Societies.