MOUSE FIBROBLAST-ACTIVATION PROTEIN - CONSERVED FAP GENE ORGANIZATIONAND BIOCHEMICAL FUNCTION AS A SERINE-PROTEASE

The human fibroblast-activation protein (FAP), a member of the serine protease family, was discovered as an inducible type-II cell-surface g lycoprotein selectively expressed by reactive stromal fibroblasts of e pithelial cancers and healing wounds. Antibodies directed against huma n FAP have a clinical use for antibody-based tumor imaging. As part of an effort to generate animal models of FAP expression in epithelial t umorigenesis and wound healing, we previously cloned the cDNA encoding the mouse FAP homolog. In this study, we used PCR/restriction-fragmen t length polymorphism, identified in interspecific back-crosses betwee n Mns musculus and Mus spretus, to map the Fap, gene locus to a region of mouse chromosome 2, known to be syntenic to the previously identif ied FAP gene locus on human chromosome 2q23. The Fap gene spans approx imately 60 kb and contains 26 exons ranging in size from 46 bp to 195 bp. This genomic organization is very similar to that of the human FAP locus. Similar to the gene encoding dipeptidyl peptidase IV (DPP IV), the nucleotides encoding the serine protease consensus motif, WGWSYGG , are split between two exons, a feature distinct from classical serin e proteases. Consistent with the similarity to DPP IV, a chimeric FAP fusion protein expressed in a baculovirus system has dipeptidyl peptid ase activity.