Skeletal casein kinase activity defect in the HYP mouse.
The Hyp mouse, a model for human X-linked hypophosphatemia (XLH), is characterized by phosphate wasting and defective mineralization. Since osteopontin (OPN) is considered pivotal for biological mineralization, we examined the biosynthesis of OPN in osteoblasts of +/Y and Hyp/Y mice. Immunoprecipitation analyses using a specific antibody to OPN revealed that Hyp/Y and +/Y osteoblasts secrete similar levels of OPN as determined by [35S]-methionine biosynthetic labeling, but a reduced phosphorylation was noted after 32P-PO4 biosynthetic labeling. Northern blot hybridization analysis of +/Y and Hyp/Y mice osteoblast mRNAs, using a cDNA probe for mouse OPN, revealed no difference in the steady state levels of osteopontin mRNA. Analysis of casein kinase II activity in +/Y and Hyp/Y mice osteoblast, kidney, heart and liver membrane 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-translation defect in the Hyp/Y mouse osteoblast which results in the under-phosphorylation of osteopontin and subsequent under-mineralization of bone matrix.
Rifas
L
L
Division of Bone and Mineral Diseases, Department of Internal Medicine, Washington University School of Medicine at Barnes-Jewish Hospital, 216 South Kingshighway Blvd., St. Louis, MO 63110 USA.
Cheng
S
S
Halstead
L R
LR
Gupta
A
A
Hruska
K A
KA
Avioli
L V
LV
D000818:Animals; D047390:Casein Kinase II; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007015:Hypophosphatemia, Familial / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D051379:Mice; D008817:Mice, Mutant Strains; D009206:Myocardium / Q000201:enzymology; D010006:Osteoblasts / Q000378:metabolism*; D053495:Osteopontin; D010750:Phosphoproteins / Q000096:biosynthesis*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000096:biosynthesis*
D010750:Phosphoproteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases