Mepe, the gene encoding a tumor-secreted protein in oncogenic hypophosphatemic osteomalacia, is expressed in bone.
The MEPE (matrix extracellular phosphoglycoprotein) gene is a strong candidate for the tumor-derived phosphaturic factor in oncogenic hypophosphatemic osteomalacia (OHO). X-linked hypophosphatemia (XLH) is phenotypically similar to OHO and results from mutations in PHEX, a putative metallopeptidase believed to process a factor(s) regulating bone mineralization and renal phosphate reabsorption. Here we report the isolation of the murine homologue of MEPE, from a bone cDNA library, that encodes a protein of 433 amino acids, 92 amino acids shorter than human MEPE. Mepe, like Phex, is expressed by fully differentiated osteoblasts and down-regulated by 1,25-(OH)2D3. In contrast to Phex, Mepe expression is markedly increased during osteoblast-mediated matrix mineralization. Greater than normal Mepe mRNA levels were observed in bone and osteoblasts derived from Hyp mice, the murine homologue of human XLH. Our data provide the first evidence that MEPE/Mepe is expressed by osteoblasts in association with mineralization.
Argiro
L
L
Genetics Unit, Shriners Hospital, Montreal, Quebec, H3G 1A6, Canada.
Desbarats
M
M
Glorieux
F H
FH
Ecarot
B
B
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D016326:Extracellular Matrix Proteins; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D005994:Glycerophosphates / Q000494:pharmacology; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D017674:Hypophosphatemia / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000150:complications / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010018:Osteomalacia / Q000209:etiology*; D010750:Phosphoproteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014018:Tissue Distribution
D016326:Extracellular Matrix Proteins; D005994:Glycerophosphates; D006023:Glycoproteins; C486579:MEPE protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; D004247:DNA; D002118:Calcium; C031463:beta-glycerophosphoric acid