ISSN:
1432-198X
Keywords:
Phosphate deprivation
;
Renal adaptation
;
X-linkedHyp mice
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The X-linkedHyp mutation, a murine homologue of X-linked hypophosphatemia in humans, is characterized by renal defects in phosphate reabsorption and vitamin D metabolism. In addition, the renal adaptive response to phosphate deprivation in mutantHyp mice differs from that of normal littermates. WhileHyp mice fed a low phosphate diet retain the capacity to exhibit a significant increase in renal brush-border membrane sodiumphosphate cotransport in vitro, the mutants fail to show an adaptive increase in maximal tubular reabsorption of phosphate per volume of glomerular filtrate (TmP/GFR) in vivo. Moreover, unlike their normal counterparts,Hyp mice respond to phosphate restriction with a fall in the serum concentration of 1,25-dihydroxyvitamin D [1,25(OH)2D] that can be ascribed to increased renal 1,25(OH)2D catabolism. The dissociation between the adaptive brush-border membrane phosphate transport response and the TmP/GFR and vitamin D responses observed inHyp mice is also apparent in X-linkedGy mice and hypophysectomized rats. Based on these findings and the notion that transport across the brush-border membrane reflects proximal tubular function, we suggest that the adaptive TmP/GFR response requires the participation of 1,25(OH)2D or a related metabolite and that a more distal segment of the nephron is the likely target for the 1,25(OH)2D-dependent increase in overall tubular phosphate conservation.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00853232
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