The genomic response of the mouse kidney to low-phosphate diet is altered in X-linked hypophosphatemia.
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 1alpha- 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.
Meyer
Martha H
MH
Orthopaedic Research Laboratory, Carolinas Medical Center, Charlotte, North Carolina 28232-2861, USA.
Dulde
Emily
E
Meyer
Ralph A
RA
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000503:physiopathology; D005838:Genotype; D007015:Hypophosphatemia, Familial / Q000235:genetics* / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008870:Microtubules / Q000378:metabolism; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D016226:Phosphorus, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis
D016226:Phosphorus, Dietary; D012333:RNA, Messenger