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Differential effects of Npt2a gene ablation and X-linked Hyp mutation on renal expression of Npt2c

Differential effects of Npt2a gene ablation and X-linked Hyp mutation on renal expression of Npt2c The present study was undertaken to define the mechanisms governing the regulation of the novel renal brush-border membrane (BBM) Na-phosphate (P i ) cotransporter designated type IIc (Npt2c). To address this issue, the renal expression of Npt2c was compared in two hypophosphatemic mouse models with impaired renal BBM Na-P i cotransport. In mice homozygous for the disrupted Npt2a gene ( Npt2 – / – ), BBM Npt2c protein abundance, relative to actin, was increased 2.8-fold compared with Npt2 +/+ littermates, whereas a corresponding increase in renal Npt2c mRNA abundance, relative to -actin, was not evident. In contrast, in X-linked Hyp mice, which harbor a large deletion in the Phex gene, the renal abundance of both Npt2c protein and mRNA was significantly decreased by 80 and 50%, respectively, relative to normal littermates. P i deprivation elicited a 2.5-fold increase in BBM Npt2c protein abundance in Npt2 +/+ mice but failed to elicit a further increase in Npt2c protein in Npt2 – / – mice. P i restriction led to an increase in BBM Npt2c protein abundance in both normal and Hyp mice without correcting its renal expression in the mutants. In summary, we report that BBM Npt2c protein expression is differentially regulated in Npt2 – / – mice and Hyp mice and that the Npt2c response to low-P i challenge differs in both hypophosphatemic mouse strains. We demonstrate that Npt2c protein is maximally upregulated in Npt2 – / – mice and suggest that Npt2c likely accounts for residual BBM Na-P i cotransport in the knockout model. Finally, our data indicate that loss of Phex function abrogates renal Npt2c protein expression. hypophosphatemia; mouse; Phex; Na-P i cotransporter type I; low phosphate Address for reprint requests and other correspondence: H. S. Tenenhouse, Montreal Children's Hospital Research Institute, 4060 Ste-Catherine St. West, Rm. 222, Montreal, Quebec, Canada H3Z 2Z3 (E-mail: [email protected] ). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Renal Physiology The American Physiological Society

Differential effects of Npt2a gene ablation and X-linked Hyp mutation on renal expression of Npt2c

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References (45)

Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0363-6127
eISSN
1522-1466
DOI
10.1152/ajprenal.00252.2003
pmid
12952859
Publisher site
See Article on Publisher Site

Abstract

The present study was undertaken to define the mechanisms governing the regulation of the novel renal brush-border membrane (BBM) Na-phosphate (P i ) cotransporter designated type IIc (Npt2c). To address this issue, the renal expression of Npt2c was compared in two hypophosphatemic mouse models with impaired renal BBM Na-P i cotransport. In mice homozygous for the disrupted Npt2a gene ( Npt2 – / – ), BBM Npt2c protein abundance, relative to actin, was increased 2.8-fold compared with Npt2 +/+ littermates, whereas a corresponding increase in renal Npt2c mRNA abundance, relative to -actin, was not evident. In contrast, in X-linked Hyp mice, which harbor a large deletion in the Phex gene, the renal abundance of both Npt2c protein and mRNA was significantly decreased by 80 and 50%, respectively, relative to normal littermates. P i deprivation elicited a 2.5-fold increase in BBM Npt2c protein abundance in Npt2 +/+ mice but failed to elicit a further increase in Npt2c protein in Npt2 – / – mice. P i restriction led to an increase in BBM Npt2c protein abundance in both normal and Hyp mice without correcting its renal expression in the mutants. In summary, we report that BBM Npt2c protein expression is differentially regulated in Npt2 – / – mice and Hyp mice and that the Npt2c response to low-P i challenge differs in both hypophosphatemic mouse strains. We demonstrate that Npt2c protein is maximally upregulated in Npt2 – / – mice and suggest that Npt2c likely accounts for residual BBM Na-P i cotransport in the knockout model. Finally, our data indicate that loss of Phex function abrogates renal Npt2c protein expression. hypophosphatemia; mouse; Phex; Na-P i cotransporter type I; low phosphate Address for reprint requests and other correspondence: H. S. Tenenhouse, Montreal Children's Hospital Research Institute, 4060 Ste-Catherine St. West, Rm. 222, Montreal, Quebec, Canada H3Z 2Z3 (E-mail: [email protected] ).

Journal

AJP - Renal Physiology – The American Physiological Society

Published: Dec 1, 2003

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