title: Phosphate transport in renal cell cultures of gy mice: evidence of a single defect in X-linked hypophosphatemia.
abstract: Although current theory holds that the murine homologs of X-linked hypophosphatemia represent mutations of two closely linked genes with distinct pathophysiological consequences, insufficient data are available to support this hypothesis. We investigated whether an intrinsic defect in renal sodium (Na+)-dependent Pi cotransport truly distinguishes gy from hyp mice. We compared Pi transport in immortalized cells from S1 and S2 segments of the renal proximal convoluted tubule (PCT) of normal and gy mice. Cells from both murine models exhibit characteristics of differentiated PCT cells including gluconeogenesis, alkaline phosphatase activity, and parathyroid hormone (PTH)- and thyrocalcitonin (TCT)-dependent adenosine 3',5'-cyclic monophosphate production. More importantly, kinetic studies reveal that cells from the PCT of gy mice have intrinsically normal Pi transport and support the hypothesis that, as in hyp mice, a humoral abnormality is likely responsible for the renal Pi wasting in this mouse model. These observations are consistent with the conclusion that gy and hyp mice do not represent mutations of two closely linked genes but rather two separate mutations of the same gene.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: T
authors.initials: T
authors.lastname: Nesbitt
authors.forename: M K
authors.initials: MK
authors.lastname: Drezner
mesh_terms: D000818:Animals; D000957:Antigens, Viral, Tumor / Q000096:biosynthesis / Q000235:genetics; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D017674:Hypophosphatemia / Q000235:genetics / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010641:Phenotype; D010710:Phosphates / Q000378:metabolism*; D013539:Simian virus 40; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D014960:X Chromosome
chemical_list: D000957:Antigens, Viral, Tumor; D002352:Carrier Proteins; D010710:Phosphates; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D000242:Cyclic AMP