Review CALL FOR PAPERS APS Conference “Understanding Renal and Cardiovascular Function Through Physiological Genomics” The genomic response of the mouse kidney to low-phosphate diet is altered in X-linked hypophosphatemia

Meyer, Martha H., Emily Dulde, and Ralph A. Meyer, Jr. The genomic response of the mouse kidney to low-phosphate diet is altered in X-linked hypophosphatemia. Physiol Genomics 18: 4–11, 2004.. First published March 30, 2004; 10.1152/physiolgenomics. 00210.2003.—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, 5-wk-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 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 and -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.