TY - JOUR
T1 - Skeletal casein kinase activity defect in the HYP mouse
AU - Rifas, L.
AU - Cheng, S. L.
AU - Halstead, L. R.
AU - Gupta, A.
AU - Hruska, K. A.
AU - Avioli, L. V.
PY - 1997/9
Y1 - 1997/9
N2 - 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-translational defect in the Hyp/Y mouse osteoblast which results in the underphosphorylation of osteopontin and subsequent under-mineralization of bone matrix.
AB - 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-translational defect in the Hyp/Y mouse osteoblast which results in the underphosphorylation of osteopontin and subsequent under-mineralization of bone matrix.
UR - http://www.scopus.com/inward/record.url?scp=0030788154&partnerID=8YFLogxK
U2 - 10.1007/s002239900331
DO - 10.1007/s002239900331
M3 - Article
C2 - 9262518
AN - SCOPUS:0030788154
SN - 0171-967X
VL - 61
SP - 256
EP - 259
JO - Calcified Tissue International
JF - Calcified Tissue International
IS - 3
ER -