Primary cultures of renal epithelial cells from X-linked hypophosphatemic (Hyp) mice express defects in phosphate transport and vitamin D metabolism.
Mutation in a gene (symbol Hyp) on the X chromosome causes hypophosphatemia in the mouse. The murine phenotype is a counterpart of X-linked hypophosphatemia in man. Both exhibit impaired renal reabsorption of phosphate in vivo. In vitro studies in the Hyp mouse have shown decreased Na+-dependent phosphate transport at the brush border membrane and abnormal mitochondrial vitamin D metabolism. To determine whether the mutant renal phenotype is intrinsic to the kidney or dependent upon putative extrinsic humoral factor(s) for its expression, we established primary cultures of renal epithelial cells from normal and Hyp male mouse kidneys. The cells are derived from proximal tubule. Initial uptake rates of phosphate and alpha-methyl-D-glucopyranoside (alpha-MG), a metabolically inert analogue of D-glucose, were measured simultaneously in confluent monolayers exhibiting epithelial polarity and tight junctions. The mean phosphate/alpha-MG uptake ratio in Hyp cultures was 82% of that in normal cells (P less than 0.01, n = 96). Moreover, the production of 24,25-dihydroxyvitamin D3 was significantly elevated in confluent cultures of Hyp cells relative to normal cells. These results imply that the Hyp gene is expressed in situ in renal epithelium and suggest that humoral factors are not necessary for the mutant renal phenotype in X-linked hypophosphatemia of mouse and man.
Bell
C L
CL
McGill University-Montreal Children's Hospital Research Institute, Department of Pediatrics, Quebec.
Tenenhouse
H S
HS
Scriver
C R
CR
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism; D007015:Hypophosphatemia, Familial / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008757:Methylglucosides / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008871:Microvilli / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D012402:Rotenone / Q000494:pharmacology; D014807:Vitamin D / Q000378:metabolism*; D014960:X Chromosome
D008757:Methylglucosides; D010710:Phosphates; D012402:Rotenone; D014807:Vitamin D