OSTEOCALCIN CLUSTER - IMPLICATIONS FOR FUNCTIONAL-STUDIES

Osteocalcin is a skeletal member of the family of extracellular minera l binding Gla protein. Osteocalcin is synthesized only by the osteobla st and it is secreted into the bone matrix at the time of bone mineral ization. The mineral binding properties of osteocalcin as well as its spatial and temporal pattern of expression suggest that it plays a rol e during bone mineralization, however until now its biological functio n is unclear. To understand osteocalcin function during skeletogenesis we mutated the two osteocalcin genes by homologous recombination in e mbryonic stem (ES) cells. Eight targeted clones were identified by Sou thern analysis using external probes. One of these clones contributed to the germ line of mouse chimera. Interbreeding of heterozygotes is c urrently in progress. Mutant mice will be useful to understand osteoca lcin function in vivo. (C) 1995 Wiley-Liss, Inc.