Cloning of the bone Gla protein gene from the teleost fish Sparus aurata. Evidence for overall conservation in gene organization and bone-specific expression from fish to man

Bone Gla protein (BGP, Osteocalcin) is a bone-specific vitamin K-dependenl protein which has been intensively studied in mammals. Although BGP is the most abundant non-collagenous protein of bone, its mode of action at the mo lecular level remains unclear. From an evolutionary point of view, the appe arance of BGP seems to parallel the appearance of hydroxyapalite-containing hone structures since it has never been found in elasmobranchs, whose skel eton is composed of calcified cartilage. Accordingly, recent work indicates that, in mammalian bone, BGP is required for adequate maturation of the hy droxyapatite crystal. Taken together, these data suggest that teleost fishe s, presumably the first vertebrates to develop a BGP-containing skeleton, m ay be a useful model to further investigate BGP function. In addition, fish offer several advantages over mammalian models, due to a large progeny, ex ternal embryonic development and transparency of larvae. In the present wor k, the BGP cDNA and gene were cloned from a teleost fish. Sparus aurata, an d its tissue distribution, pattern of developmental expression and evolutio nary pathways analyzed. The molecular organization of the Sparus BGP (spBGP ) gene is similar to mammalian BGP gents, and its expression throughout dev elopment follows the onset of calcification. The spBGP gene encodes a pre p ropeptide of 97 amino acid residues, expressed only in bone and showing ext ensive homology to its mammalian homologs. Phylogenetic analysis of the ava ilable BGP sequences supports the hypothesis that all BGPs have a single or igin and share a common ancestor with a related vitamin K-dependent protein (Matrix Gla protein). (C) 2001 Elsevier Science B.V. All rights reserved.