IDENTIFICATION OF THE HUMAN KLOTHO GENE AND ITS 2 TRANSCRIPTS ENCODING MEMBRANE AND SECRETED KLOTHO PROTEIN

Inactivation of the klotho (kl) gene in mice results in multiple disor ders that resemble human aging. The mouse hi gene encodes a novel sing le-pass membrane protein with homology to beta-glucosidases. In this s tudy, we have isolated a human homologue of the kl gene and determined its gene structure. The human kl gene is composed of 5 exons and rang es over 50 kb on chromosome 13q12. We have further identified two tran scripts that encode a membrane or secreted protein. These transcripts arise from a single kl gene through alternative RNA splicing. Expressi on of the putative secreted form predominates over that of the membran e form. The present study provides fundamental information necessary f or further analyses of the human kl gene and its functions. (C) 1998 A cademic Press.