SKELETAL CASEIN KINASE-ACTIVITY DEFECT IN THE HYP MOUSE

The Hyp mouse, a model for human X-linked hypophosphatemia (XLH), is c haracterized by phosphate wasting and defective mineralization. Since osteopontin (OPN) is considered pivotal for biological mineralization, rye examined the biosynthesis of OPN in osteoblasts of +/Y and Hyp/Y mice. Immunoprecipitation analyses using a specific antibody to OPN re vealed that Hyp/Y and +/Y osteoblasts secrete similar levels of OPN as determined but [S-35]-methionine biosynthetic labeling, but a reduced phosphorylation was noted after P-32-PO4 biosynthetic labeling. North ern blot hybridization analysis of +/Y and Hyp/Y mice osteoblast mRNAs , using a cDNA probe for mouse OPN, revealed no difference in the stea dy state levels of osteopontin mRNA. Analysis of casein kinase II acti vity in +/Y and Hyp/Y mice osteoblast, kidney, heart and liver membran e fractions revealed that casein kinase II activity in the Hyp/Y mice osteoblasts and kidney is only 35%-50%, respectively, of that of the /Y mice tissues. The accumulated data are consistent with a post-trans lational defect in the Hyp/Y mouse osteoblast which results in the und erphosphorylation of osteopontin and subsequent undermineralization of bone matrix.