Abstract
In order to obtain a better understanding of the molecular mechanisms involved in phosphate reabsorption and vitamin D hormone production by mammalian kidney, we have devoted our efforts to the study of a mutant mouse model (Hyp). Studies from our laboratory have demonstrated that Na+-dependent phosphate transport is significantly reduced in renal brush border membrane vesicles derived fromHyp mice and that the regulation of the renal mitochondrial enzymes which metabolize 25-hydroxyvitamin D3 (25-OH-D3) is impaired in the mutant strain. The demonstration of abnormal phosphate transport and 25-OH-D3 metabolism in proximal tubule cells derived fromHyp kidney after 6–8 days in culture indicates that the mutant renal phenotype is independent of circulating factors and, therefore, intrinsic to the kidney. However, the precise relationship between these two proximal tubular abnormalities is poorly understood. Because theHyp mutation segregates as a Mendelian trait, it is very likely that one mutant gene is responsible for the biochemical and clinical phenotype. Several hypotheses are put forth to explain the nature of the primary mutation in theHyp mouse.
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Tenenhouse, H.S. Vitamin D metabolism and phosphate transport in developing kidney: effect of diet and mutation. Pediatr Nephrol 2, 171–175 (1988). https://doi.org/10.1007/BF00870400
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DOI: https://doi.org/10.1007/BF00870400