title: Effect of phosphate supplementation on the expression of the mutant phenotype in murine X-linked hypophosphatemic rickets.
abstract: The X-linked Hyp mouse, a murine homologue of X-linked hypophosphatemia in humans, is characterized by rachitic bone disease, hypophosphatemia, impaired renal brush-border membrane Na(+)-phosphate cotransport and abnormal regulation of renal vitamin D metabolism. We demonstrated that short-term phosphate supplementation decreases renal 1,25-dihydroxyvitamin D3 (1,25-(OH)2D) catabolism and increases serum 1,25-(OH)2D levels in Hyp mice (Tenenhouse & Jones 1990). In the present study, we compared several other parameters in normal and Hyp mice fed control (1%) and high (1.6%) phosphate diets for 4 days. Phosphate supplementation significantly raised serum phosphate levels and decreased renal brush-border membrane Na(+)-phosphate but not Na(+)-glucose, cotransport in both genotypes (67% of control diet, p < 0.05). However, under both dietary conditions, the phosphate/glucose transport ratio was significantly reduced in Hyp mice (58% of normal littermates, p < 0.05). Renal PTH-stimulated cAMP accumulation, which was significantly blunted in Hyp mice compared to normal mice under control dietary conditions (p < 0.05), was not altered by phosphate supplementation in either genotype. Serum alkaline phosphatase activity was significantly higher than normal in Hyp mice on the control diet and was further increased in mutants but not in normals fed the high phosphate diet (p < 0.05). Measurements of serum bilirubin and electrophoresis of serum alkaline phosphatase suggested that the elevation in serum alkaline phosphatase activity in phosphate-supplemented Hyp mice represents the bone-derived isozyme.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pediatrics, McGill University-Montreal Children's Hospital, Research Institute, Quebec, Canada.
authors.forename: H S
authors.initials: HS
authors.lastname: Tenenhouse
authors.forename: J
authors.initials: J
authors.lastname: Martel
authors.forename: J
authors.initials: J
authors.lastname: Rubin
authors.forename: N
authors.initials: N
authors.lastname: Harvey
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004100:Dihydroxycholecalciferols / Q000097:blood; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D005838:Genotype; D007015:Hypophosphatemia, Familial / Q000178:diet therapy* / Q000235:genetics; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000187:drug effects; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D010281:Parathyroid Hormone / Q000494:pharmacology; D010641:Phenotype; D010710:Phosphates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016226:Phosphorus, Dietary / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012964:Sodium / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D004100:Dihydroxycholecalciferols; D009004:Monosaccharide Transport Proteins; D010281:Parathyroid Hormone; D010710:Phosphates; D016226:Phosphorus, Dietary; D012964:Sodium; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D002117:Calcitriol; D001663:Bilirubin