PHOSPHATE-TRANSPORT IN RENAL-CELL CULTURES OF GY MICE - EVIDENCE OF ASINGLE DEFECT IN X-LINKED HYPOPHOSPHATEMIA

Although current theory holds that the murine homologs of X-linked hyp ophosphatemia represent mutations of two closely linked genes with dis tinct pathophysiological consequences, insufficient data are available to support this hypothesis. We investigated whether an intrinsic defe ct in renal sodium (Na+)-dependent P-i cotransport truly distinguishes gy from hyp mice. We compared P-i transport in immortalized cells fro m S1 and S2 segments of the renal proximal convoluted tubule (PCT) of normal and gy mice. Cells from both murine models exhibit characterist ics of differentiated PCT cells including gluconeogenesis, alkaline ph osphatase 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 mic e have intrinsically normal P-i transport and support the hypothesis t hat, as in hyp mice, a humoral abnormality is likely responsible for t he renal P-i wasting in this mouse model. These observations are consi stent with the conclusion that gy and hyp mice do not represent mutati ons of two closely linked genes but rather two separate mutations of t he same gene.