Primary Cultures ofRenalEpithelial Cells fromX-linked Hypophosphatemic (Hyp)MiceExpress Defects in Phosphate Transport andVitamin D Metabolism

Summary Mutation ina gene (symbol Hyp)on theX chromosome causeshypophosphatemia inthemouse. Themurine phenotype isa counterpartofX-linked hypophosphatemia inman. Bothexhibit impaired renal reabsorption ofphosphate invivo. Invitro studies intheHypmouse haveshowndecreased Na+-dependent phosphate transport atthebrush border membrane andabnormal mitochondrial vitamin D metabolism. Todetermine whether themutantrenal phenotype isintrinsic tothekidney or dependent upon putative extrinsic humoral factor(s) foritsexpression, we established primary cultures ofrenal epithelial cells from normal andHypmalemouse kidneys. Thecells arederived fromproximal tubule. Initial uptake ratesof phosphate anda-methyl-D-glucopyranoside (a-MG), a metabolically inert analogue ofD-glucose, were measured simultaneously inconfluent monolayers exhibiting epithelial polarity andtight junctions. The mean phosphate/a-MG uptake ratio inHypcultures was 82%ofthat innormal cells (P< 0.01, n = 96). Moreover, theproduction of24,25-dihydroxyvitamin D3was significantly elevated inconfluent cultures of Hypcells relative tonormal cells. Theseresults imply thattheHypgene isexpressed insitu inrenal epithelium andsuggestthathumoral factors arenotnecessaryforthemutantrenal phenotype inX-linked hypophosphatemia ofmouse andman.