Physiol. Genomics AJP: Heart and Circulatory Physiology
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Physiol. Genomics (March 30, 2004). doi:10.1152/physiolgenomics.00210.2003
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Submitted on December 12, 2003
Accepted on March 25, 2004

The genomic response of the mouse kidney to low phosphate diet is altered in X-linked hypophosphatemia

Martha H Meyer1, Emily Dulde1, and Ralph A Meyer, Jr.1*

1 Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, NC, USA

* To whom correspondence should be addressed. E-mail: rmeyer{at}carolinas.org.

The mechanism for the renal adaptation to low phosphate diets is not well understood. Whether the Hyp mutation of the Phex gene blocks this adaptation is also not clear. To gain further insight into this, five week-old normal and Hyp mice were fed a control (1.0% P) or low phosphate diet (0.03% P) for 3-5 days. Renal RNA was hybridized to Affymetrix U74Av2 microarrays (5 arrays/group). Of the 5,719 detectable genes on each array, 290 responded significantly (P < 0.01) to low phosphate diet in normal mice. This was reduced significantly (P < 0.001) to 7 in the Hyp mice. This suggested that the adaptations of the normal kidney to a low phosphate environment were blocked by the Hyp mutation. The Npt2 phosphate transporter, vitamin D 1{alpha}- and 24-hydroxylases, and calbindins D9K and D28K responded in the expected fashion. Genes with significant (P < 0.05) diet-by-genotype interaction were analyzed by GenMAPP and MAPPFinder. This revealed a cluster of differentially expressed genes associated with microtubule-based processes. Most alpha and beta tubulins and most kinesins had responses to low phosphate diet in normal mice which were abolished or reversed in Hyp mice. In summary, renal adaptation to low phosphate diet involved changes in the mRNA expression of specific genes. Disruption of these responses in Hyp mice may contribute to their abnormal phosphate homeostasis.




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