Phex

Summary

Gene Symbol: Phex
Description: phosphate regulating endopeptidase homolog, X-linked
Alias: HPDR, HPDR1, Hyp, PEX, metalloendopeptidase homolog PEX, Metalloendopeptidase homolog PEX (Phosphate regulating neutral endopeptidase) (X-linked hypophosphatemia protein) (HYP) (Vitamin D-resistant hypophosphatemic rickets protein), X-linked hypophosphatemia protein, X-linked phosphate regulating endopeptidase, phosphate regulating gene with homologies to endopeptidases on the X chromosome (hypophosphatemia, vitamin D resistant rickets), phosphate regulating neutral endopeptidase, vitamin D-resistant hypophosphatemic rickets protein
Species: mouse
Products:     Phex

Top Publications

  1. Martin A, Liu S, David V, Li H, Karydis A, Feng J, et al. Bone proteins PHEX and DMP1 regulate fibroblastic growth factor Fgf23 expression in osteocytes through a common pathway involving FGF receptor (FGFR) signaling. FASEB J. 2011;25:2551-62 pubmed publisher
    ..Inactivating mutations of the endopeptidase PHEX or the SIBLING protein DMP1 result in equivalent intrinsic bone mineralization defects and increased Fgf23 ..
  2. Megerian C, Semaan M, Aftab S, Kisley L, Zheng Q, Pawlowski K, et al. A mouse model with postnatal endolymphatic hydrops and hearing loss. Hear Res. 2008;237:90-105 pubmed publisher
    ..A search for such a model led us to the Phex Hyp-Duk mouse, a mutant allele of the Phex gene causing X-linked hypophosphatemic rickets...
  3. Sitara D, Razzaque M, Hesse M, Yoganathan S, Taguchi T, Erben R, et al. Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient mice. Matrix Biol. 2004;23:421-32 pubmed
    ..that Fgf-23 is upstream of the phosphate regulating gene with homologies to endopeptidases on the X chromosome (Phex) and that the increased plasma Fgf-23 levels in Hyp mice (and in XLH patients) may be at least partially ..
  4. Syal A, Schiavi S, Chakravarty S, Dwarakanath V, Quigley R, Baum M. Fibroblast growth factor-23 increases mouse PGE2 production in vivo and in vitro. Am J Physiol Renal Physiol. 2006;290:F450-5 pubmed
    ..Recently, we demonstrated that Hyp mice have greater urinary PGE2 levels compared with C57/B6 mice and that indomethacin administration in vivo and in ..
  5. Eicher E, Southard J, Scriver C, Glorieux F. Hypophosphatemia: mouse model for human familial hypophosphatemic (vitamin D-resistant) rickets. Proc Natl Acad Sci U S A. 1976;73:4667-71 pubmed
    A new dominant mutation in the laboratory mouse, hypophosphatemia (gene symbol Hyp), has been identified. The Hyp gene is located on the X-chromosome and maps at the distal end...
  6. Li H, Martin A, David V, Quarles L. Compound deletion of Fgfr3 and Fgfr4 partially rescues the Hyp mouse phenotype. Am J Physiol Endocrinol Metab. 2011;300:E508-17 pubmed publisher
    ..In studies using the Hyp mouse model, which displays FGF23-mediated hypophosphatemia and aberrant vitamin D, deletion of Fgfr3 or Fgfr4 ..
  7. Du L, Desbarats M, Viel J, Glorieux F, Cawthorn C, Ecarot B. cDNA cloning of the murine Pex gene implicated in X-linked hypophosphatemia and evidence for expression in bone. Genomics. 1996;36:22-8 pubmed
    The recently identified human PEX gene apparently encodes for a neutral endopeptidase that is mutated in patients with X-linked hypophosphatemia...
  8. Karunaratne A, Esapa C, Hiller J, Boyde A, Head R, Bassett J, et al. Significant deterioration in nanomechanical quality occurs through incomplete extrafibrillar mineralization in rachitic bone: evidence from in-situ synchrotron X-ray scattering and backscattered electron imaging. J Bone Miner Res. 2012;27:876-90 pubmed publisher
    ..missense Trp314Arg mutation of the phosphate regulating gene with homologies to endopeptidase on the X chromosome (Phex) and with features consistent with X-linked hypophosphatemic rickets (XLHR) in man, was investigated using in situ ..
  9. Liu S, Tang W, Zhou J, Vierthaler L, Quarles L. Distinct roles for intrinsic osteocyte abnormalities and systemic factors in regulation of FGF23 and bone mineralization in Hyp mice. Am J Physiol Endocrinol Metab. 2007;293:E1636-44 pubmed
    ..hypophosphatemia (XLH) is characterized by hypophosphatemia and impaired mineralization caused by mutations of the PHEX endopeptidase (phosphate-regulating gene with homologies to endopeptidases on the X chromosome), which leads to the ..

More Information

Publications90

  1. Carpinelli M, Wicks I, Sims N, O Donnell K, Hanzinikolas K, Burt R, et al. An ethyl-nitrosourea-induced point mutation in phex causes exon skipping, x-linked hypophosphatemia, and rickets. Am J Pathol. 2002;161:1925-33 pubmed
    ..1 (Ska1), was shown to be a single base pair mutation in a splice donor site immediately following exon 8 of the Phex (phosphate-regulating gene with homologies to endopeptidases located on the X-chromosome) gene...
  2. Liu S, Zhou J, Tang W, Jiang X, Rowe D, Quarles L. Pathogenic role of Fgf23 in Hyp mice. Am J Physiol Endocrinol Metab. 2006;291:E38-49 pubmed
    Inactivating mutations of the PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) endopeptidase, the disease-causing gene in X-linked hypophosphatemia (XLH), results in increased circulating levels of ..
  3. Miyagawa K, Yamazaki M, Kawai M, Nishino J, Koshimizu T, Ohata Y, et al. Dysregulated gene expression in the primary osteoblasts and osteocytes isolated from hypophosphatemic Hyp mice. PLoS ONE. 2014;9:e93840 pubmed publisher
    Osteocytes express multiple genes involved in mineral metabolism including PHEX, FGF23, DMP1 and FAM20C...
  4. Strom T, Francis F, Lorenz B, Böddrich A, Econs M, Lehrach H, et al. Pex gene deletions in Gy and Hyp mice provide mouse models for X-linked hypophosphatemia. Hum Mol Genet. 1997;6:165-71 pubmed
    ..b>Hyp and Gy mice both have X-linked hypophosphatemic rickets, although genetic data and the different phenotypic spectra ..
  5. Perwad F, Azam N, Zhang M, Yamashita T, Tenenhouse H, Portale A. Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice. Endocrinology. 2005;146:5358-64 pubmed
    ..demonstrate that dietary Pi regulates the serum FGF-23 concentration in mice, and such regulation is independent of phex function...
  6. Barros N, Hoac B, Neves R, Addison W, Assis D, Murshed M, et al. Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia. J Bone Miner Res. 2013;28:688-99 pubmed publisher
    ..wasting, hypophosphatemia, osteomalacia, and tooth abscesses-is caused by mutations in the zinc-metallopeptidase PHEX gene (phosphate-regulating gene with homologies to endopeptidase on the X chromosome)...
  7. Liu S, Tang W, Fang J, Ren J, Li H, Xiao Z, et al. Novel regulators of Fgf23 expression and mineralization in Hyp bone. Mol Endocrinol. 2009;23:1505-18 pubmed publisher
    We used gene array analysis of cortical bone to identify Phex-dependent gene transcripts associated with abnormal Fgf23 production and mineralization in Hyp mice...
  8. Yuan B, Takaiwa M, Clemens T, Feng J, Kumar R, ROWE P, et al. Aberrant Phex function in osteoblasts and osteocytes alone underlies murine X-linked hypophosphatemia. J Clin Invest. 2008;118:722-34 pubmed publisher
    Patients with X-linked hypophosphatemia (XLH) and the hyp-mouse, a model of XLH characterized by a deletion in the Phex gene, manifest hypophosphatemia, renal phosphate wasting, and rickets/osteomalacia...
  9. Xiong X, Qi X, Ge X, Gu P, Zhao J, Zhao Q, et al. A novel Phex mutation with defective glycosylation causes hypophosphatemia and rickets in mice. J Biomed Sci. 2008;15:47-59 pubmed
    ..The new mutation was mapped to X-chromosome between 65.4 cM and 66.6 cM, where Phex gene resides...
  10. Addison W, Masica D, Gray J, McKee M. Phosphorylation-dependent inhibition of mineralization by osteopontin ASARM peptides is regulated by PHEX cleavage. J Bone Miner Res. 2010;25:695-705 pubmed publisher
    ..X-linked hypophosphatemia caused by inactivating mutations of the PHEX gene results in elevated mineralization-inhibiting MEPE-derived ASARM peptides...
  11. Yuan B, Feng J, BOWMAN S, Liu Y, Blank R, Lindberg I, et al. Hexa-D-arginine treatment increases 7B2•PC2 activity in hyp-mouse osteoblasts and rescues the HYP phenotype. J Bone Miner Res. 2013;28:56-72 pubmed publisher
    ..mutations of the "phosphate regulating gene with homologies to endopeptidases on the X chromosome" (PHEX/Phex) underlie disease in patients with X-linked hypophosphatemia (XLH) and the hyp-mouse, a murine homologue of ..
  12. Ichikawa S, Austin A, Gray A, Econs M. A Phex mutation in a murine model of X-linked hypophosphatemia alters phosphate responsiveness of bone cells. J Bone Miner Res. 2012;27:453-60 pubmed publisher
    Mutations in the PHEX gene cause X-linked hypophosphatemia (XLH)...
  13. Beck L, Soumounou Y, Martel J, Krishnamurthy G, Gauthier C, Goodyer C, et al. Pex/PEX tissue distribution and evidence for a deletion in the 3' region of the Pex gene in X-linked hypophosphatemic mice. J Clin Invest. 1997;99:1200-9 pubmed
    b>PEX, a phosphate-regulating gene with homology to endopeptidases on the X chromosome, was recently identified as the candidate gene for X-linked hypophosphatemia...
  14. Brownstein C, Zhang J, Stillman A, Ellis B, Troiano N, Adams D, et al. Increased bone volume and correction of HYP mouse hypophosphatemia in the Klotho/HYP mouse. Endocrinology. 2010;151:492-501 pubmed publisher
    Inactivating mutations of PHEX cause X-linked hypophosphatemia and result in increased circulating fibroblast growth factor 23 (FGF23). FGF23 action is dependent upon Klotho, which converts FGF receptor 1 into an FGF23-specific receptor...
  15. Liu S, Tang W, Zhou J, Stubbs J, Luo Q, Pi M, et al. Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. J Am Soc Nephrol. 2006;17:1305-15 pubmed
    ..In the Hyp-mouse homologue of X-linked hypophosphatemic rickets, administration of 1,25(OH)(2)D(3) further increased ..
  16. Xiao Z, Crenshaw M, Guo R, Nesbitt T, Drezner M, Quarles L. Intrinsic mineralization defect in Hyp mouse osteoblasts. Am J Physiol. 1998;275:E700-8 pubmed
    ..This defect is shared by Hyp mice, the murine homologue of the human disease, in which a 3' Pex deletion has been documented...
  17. Lorenz Depiereux B, Guido V, Johnson K, Zheng Q, Gagnon L, Bauschatz J, et al. New intragenic deletions in the Phex gene clarify X-linked hypophosphatemia-related abnormalities in mice. Mamm Genome. 2004;15:151-61 pubmed
    X-linked hypophosphatemic rickets (XLH) in humans is caused by mutation in the PHEX gene. Previously, three mutations in the mouse Phex gene have been reported: Phex(Hyp), Gy, and Phex(Ska1)...
  18. Erben R, Mayer D, Weber K, Jonsson K, Juppner H, Lanske B. Overexpression of human PHEX under the human beta-actin promoter does not fully rescue the Hyp mouse phenotype. J Bone Miner Res. 2005;20:1149-60 pubmed
    XLH in humans and the Hyp phenotype in mice are caused by inactivating Phex mutations...
  19. Lorenz B, Francis F, Gempel K, Böddrich A, Josten M, Schmahl W, et al. Spermine deficiency in Gy mice caused by deletion of the spermine synthase gene. Hum Mol Genet. 1998;7:541-7 pubmed
    ..X-linked hypophosphatemic rickets and have been shown to be deleted for the 5' and 3' end of the mouse homolog of PHEX (phosphate regulating gene with homologies to endopeptidases on the X chromosome; formerly called PEX), ..
  20. Econs M, Francis F. Positional cloning of the PEX gene: new insights into the pathophysiology of X-linked hypophosphatemic rickets. Am J Physiol. 1997;273:F489-98 pubmed
    ..Positional cloning studies have led to the identification of a gene, PEX, which is responsible for the disorder...
  21. Berning A, Eicher E, Paul W, Scher I. Mapping of the X-linked immune deficiency mutation (xid) of CBA/N mice. J Immunol. 1980;124:1875-7 pubmed
    ..We have determined that xid is situated on the X-chromosome between the genes Ta (tabby) and Hyp (hypophosphatemia), genetic distances being Ta-6.6 +/- 1.8-xid-12.2 +/- 2.3-Hyp.
  22. Sabrautzki S, Rubio Aliaga I, Hans W, Fuchs H, Rathkolb B, Calzada Wack J, et al. New mouse models for metabolic bone diseases generated by genome-wide ENU mutagenesis. Mamm Genome. 2012;23:416-30 pubmed publisher
    ..Fifteen mutations among three genes (Phex, Casr, and Alpl) have been identified by positional-candidate gene approaches and one mutation of the Asgr1 gene, ..
  23. Nakagawa N, Ghishan F. Transport of phosphate by plasma membranes of the jejunum and kidney of the mouse model of hypophosphatemic vitamin D-resistant rickets. Proc Soc Exp Biol Med. 1993;203:328-35 pubmed
    ..to investigate phosphate transport across the enterocyte and the renal tubule cells of the hypophosphatemic (Hyp) mice model...
  24. Koehne T, Marshall R, Jeschke A, Kahl Nieke B, Schinke T, Amling M. Osteopetrosis, osteopetrorickets and hypophosphatemic rickets differentially affect dentin and enamel mineralization. Bone. 2013;53:25-33 pubmed publisher
    ..and quantitative backscattered electron imaging (qBEI) to compare the dental phenotypes of Src(-/-), oc/oc and Hyp(-/0) mice, which serve as models for OP, OPR and hypophosphatemic rickets, respectively...
  25. Beck L, Tenenhouse H, Meyer R, Meyer M, Biber J, Murer H. Renal expression of Na+-phosphate cotransporter mRNA and protein: effect of the Gy mutation and low phosphate diet. Pflugers Arch. 1996;431:936-41 pubmed
    The X-linked Gy mutation is closely linked, but not allelic, to Hyp and is characterized by rickets, hypophosphatemia, decreased renal tubular maximum for phosphate (Pi) reabsorption (TmP) and a specific reduction in renal brush-border ..
  26. Addison W, Nakano Y, Loisel T, Crine P, McKee M. MEPE-ASARM peptides control extracellular matrix mineralization by binding to hydroxyapatite: an inhibition regulated by PHEX cleavage of ASARM. J Bone Miner Res. 2008;23:1638-49 pubmed publisher
    ..an inactivating mutation of the phosphate-regulating gene with homologies to endopeptidases on the X-chromosome (Phex) gene have bones with increased matrix extracellular phosphoglycoprotein (MEPE)...
  27. Sabbagh Y, Carpenter T, Demay M. Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. Proc Natl Acad Sci U S A. 2005;102:9637-42 pubmed
    ..were examined: diet-induced hypophosphatemia/hypercalcemia and hypophosphatemia secondary to mutations in the Phex gene. The former model is associated with suppressed parathyroid hormone levels as a consequence of hypercalcemia...
  28. Tenenhouse H, Martel J, Rubin J, Harvey N. Effect of phosphate supplementation on the expression of the mutant phenotype in murine X-linked hypophosphatemic rickets. Bone. 1994;15:677-83 pubmed
    The X-linked Hyp mouse, a murine homologue of X-linked hypophosphatemia in humans, is characterized by rachitic bone disease, hypophosphatemia, impaired renal brush-border membrane Na(+)-phosphate cotransport and abnormal regulation of ..
  29. Ma Y, Samaraweera M, Cooke Hubley S, Kirby B, Karaplis A, Lanske B, et al. Neither absence nor excess of FGF23 disturbs murine fetal-placental phosphorus homeostasis or prenatal skeletal development and mineralization. Endocrinology. 2014;155:1596-605 pubmed publisher
    ..Cyp24a1 was significantly reduced in Fgf23 null kidneys and was significantly increased in Phex null placentas and fetal kidneys. Phex null kidneys also showed reduced expression of Klotho...
  30. Boneh A, Reade T, Scriver C, Rishikof E. Audiometric evidence for two forms of X-linked hypophosphatemia in humans, apparent counterparts of Hyp and Gy mutations in mouse. Am J Med Genet. 1987;27:997-1003 pubmed
    Two forms of X-linked hypophosphatemia occur in the mouse. One form, caused by the Hyp gene, is a counterpart of human X-linked hypophosphatemic "vitamin D-resistant rickets"...
  31. Ruchon A, Tenenhouse H, Marcinkiewicz M, Siegfried G, Aubin J, DesGroseillers L, et al. Developmental expression and tissue distribution of Phex protein: effect of the Hyp mutation and relationship to bone markers. J Bone Miner Res. 2000;15:1440-50 pubmed
    Mutations in PHEX, a phosphate-regulating gene with homology to endopeptidases on the X chromosome, are responsible for X-linked hypophosphatemia (XLH)...
  32. Kay G, Ashworth A, Penny G, Dunlop M, Swift S, Brockdorff N, et al. A candidate spermatogenesis gene on the mouse Y chromosome is homologous to ubiquitin-activating enzyme E1. Nature. 1991;354:486-9 pubmed
    ..These Y-linked genes may form part of a coregulated group of genes which function during spermatogenesis. ..
  33. Zelenchuk L, Hedge A, Rowe P. SPR4-peptide alters bone metabolism of normal and HYP mice. Bone. 2015;72:23-33 pubmed publisher
    ASARM-peptides are substrates and ligands for PHEX, the gene responsible for X-linked hypophosphatemic rickets (HYP)...
  34. Beamer W, Wilson M, DeLuca H. Successful treatment of genetically hypophosphatemic mice by 1 alpha-hydroxyvitamin D3 but not 1,25-dihydroxyvitamin D3. Endocrinology. 1980;106:1949-55 pubmed
    The X-linked hypophosphatemia (Hyp) mutation in the mouse, a model for X-linked familial hypophosphatemic rickets in man, is characterized by defective phosphate transport...
  35. Tenenhouse H, Henry H. Protein kinase activity and protein kinase inhibitor in mouse kidney: effect of the X-linked Hyp mutation and vitamin D status. Endocrinology. 1985;117:1719-26 pubmed
    ..kinase inhibitor activity were examined in renal homogenates and 20,000 X g supernatant fractions of normal and Hyp mice...
  36. Kay G, Thakker R, Rastan S. Determination of a molecular map position for Hyp using a new interspecific backcross produced by in vitro fertilization. Genomics. 1991;11:651-7 pubmed
    ..a Mus spretus/Mus musculus domesticus interspecific backcross segregating for two X-linked mutant genes, Ta and Hyp, using in vitro fertilization...
  37. O Doherty P, DeLuca H, Eicher E. Lack of effect of vitamin D and its metabolites on intestinal phosphate transport in familial hypophosphatemia of mice. Endocrinology. 1977;101:1325-30 pubmed
    ..The results obtained are consistent with the hypothesis that the primary metabolic disturbance in familial hypophosphatemia involves a defect in phosphate transport mechanisms. ..
  38. Onishi T, Ogawa T, Hayashibara T, Hoshino T, Okawa R, Ooshima T. Hyper-expression of osteocalcin mRNA in odontoblasts of Hyp mice. J Dent Res. 2005;84:84-8 pubmed
    The Hyp mouse is a murine homologue of human X-linked hypophosphatemia that displays hypo-mineralization in bone and dentin...
  39. Nesbitt T, Econs M, Byun J, Martel J, Tenenhouse H, Drezner M. Phosphate transport in immortalized cell cultures from the renal proximal tubule of normal and Hyp mice: evidence that the HYP gene locus product is an extrarenal factor. J Bone Miner Res. 1995;10:1327-33 pubmed
    ..Cells from SV40 transgenic normal and Hyp mice exhibit characteristics of differentiated proximal tubule cells including gluconeogenesis and alkaline ..
  40. Meyer M, Dulde E, Meyer R. The genomic response of the mouse kidney to low-phosphate diet is altered in X-linked hypophosphatemia. Physiol Genomics. 2004;18:4-11 pubmed
    ..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...
  41. Ecarot B, Glorieux F, Desbarats M, Travers R, Labelle L. Effect of 1,25-dihydroxyvitamin D3 treatment on bone formation by transplanted cells from normal and X-linked hypophosphatemic mice. J Bone Miner Res. 1995;10:424-31 pubmed
    Bone cells isolated from the Hyp mouse, the murine homologue for hypophosphatemic vitamin D-resistant rickets, produce abnormal bone when transplanted to either normal or phosphate-supplemented Hyp mice...
  42. Wang L, Du L, Ecarot B. Evidence for Phex haploinsufficiency in murine X-linked hypophosphatemia. Mamm Genome. 1999;10:385-9 pubmed
    Mutations in the PHEX gene (phosphate-regulating gene with homology to endopeptidases on the X-chromosome) are responsible for X-linked hypophosphatemia (HYP)...
  43. Tenenhouse H. X-linked hypophosphataemia: a homologous disorder in humans and mice. Nephrol Dial Transplant. 1999;14:333-41 pubmed
    ..mutant gene has been identified in XLH patients, by positional cloning, and in Hyp and Gy mice, and was designated PHEX/Phex to signify a PHosphate-regulating gene with homology to Endopeptidases on the X chromosome...
  44. Collins J, Scheving L, Ghishan F. Decreased transcription of the sodium-phosphate transporter gene in the hypophosphatemic mouse. Am J Physiol. 1995;269:F439-48 pubmed
    ..against the mouse Na(+)-Pi transporter, revealed a predominant band at 87 kDa in normal and hypophosphatemic (Hyp) mice. The intensity of this band was reduced in the Hyp mouse by 4.5-fold (Hyp/normal = 0.22 +/- 0...
  45. Rifas L, Dawson L, Halstead L, Roberts M, Avioli L. Phosphate transport in osteoblasts from normal and X-linked hypophosphatemic mice. Calcif Tissue Int. 1994;54:505-10 pubmed
    ..Utilizing a mouse model (Hyp) of XLH, which demonstrates biological abnormalities and skeletal defects of XLH, we analyzed sodium-dependent ..
  46. Muller Y, Collins J, Ghishan F. Genetic screening for X-linked hypophosphatemic mice and ontogenic characterization of the defect in the renal sodium-phosphate transporter. Pediatr Res. 1998;44:633-8 pubmed
    ..Mutation of the PEX gene has been linked to human and murine Hyp rickets...
  47. Fong H, Chu E, Tompkins K, Foster B, Sitara D, Lanske B, et al. Aberrant cementum phenotype associated with the hypophosphatemic hyp mouse. J Periodontol. 2009;80:1348-54 pubmed publisher
    ..Mutations in the phosphate-regulating gene with homologies to endopeptidases on the X chromosome (Phex) cause X-linked hypophosphatemia, characterized by rickets, osteomalacia, and hypomineralized dentin formation, a ..
  48. Collins J, Bulus N, Ghishan F. Sodium-phosphate transporter adaptation to dietary phosphate deprivation in normal and hypophosphatemic mice. Am J Physiol. 1995;268:G917-24 pubmed
    The X-linked hypophosphatemic (Hyp) mouse is a model for hypophosphatemic vitamin D-resistant rickets and is a homologue of human X-linked hypophosphatemia...
  49. Fujiwara I, Aravindan R, Horst R, Drezner M. Abnormal regulation of renal 25-hydroxyvitamin D-1alpha-hydroxylase activity in X-linked hypophosphatemia: a translational or post-translational defect. J Bone Miner Res. 2003;18:434-42 pubmed
    The hyp mouse exhibits abnormal metabolic/hormonal regulation of renal 25(OH)D-1alpha-hydroxylase activity. Whether this results from aberrant transcriptional regulation of the 1alpha-hydroxylase gene, CYP27B1, remains unknown...
  50. Bai X, Miao D, Goltzman D, Karaplis A. Early lethality in Hyp mice with targeted deletion of Pth gene. Endocrinology. 2007;148:4974-83 pubmed
    Although increased circulating levels of PTH with mild hypocalcemia has been reported in Hyp mice, hyperparathyroidism in X-linked hypophosphatemic rickets is postulated to arise from the standard use of phosphate salts, which induce ..
  51. Majewski P, Thurston R, Ramalingam R, Kiela P, Ghishan F. Cooperative role of NF-{kappa}B and poly(ADP-ribose) polymerase 1 (PARP-1) in the TNF-induced inhibition of PHEX expression in osteoblasts. J Biol Chem. 2010;285:34828-38 pubmed publisher
    ..The PHEX gene encodes a zinc endopeptidase expressed in osteoblasts and contributes to bone mineralization...
  52. Zhang M, Ranch D, Pereira R, Armbrecht H, Portale A, Perwad F. Chronic inhibition of ERK1/2 signaling improves disordered bone and mineral metabolism in hypophosphatemic (Hyp) mice. Endocrinology. 2012;153:1806-16 pubmed publisher
    The X-linked hypophosphatemic (Hyp) mouse carries a loss-of-function mutation in the phex gene and is characterized by hypophosphatemia due to renal phosphate (Pi) wasting, inappropriately suppressed 1,25-dihydroxyvitamin D [1,25(OH)?D] ..
  53. Ma Y, Kirby B, Fairbridge N, Karaplis A, Lanske B, Kovacs C. FGF23 Is Not Required to Regulate Fetal Phosphorus Metabolism but Exerts Effects Within 12 Hours After Birth. Endocrinology. 2017;158:252-263 pubmed publisher
    ..However, FGF23 may not be important during fetal development. FGF23 deficiency (Fgf23 null) and FGF23 excess (Phex null) did not alter fetal phosphorus or skeletal parameters...
  54. Bai X, Miao D, Xiao S, Qiu D, St Arnaud R, Petkovich M, et al. CYP24 inhibition as a therapeutic target in FGF23-mediated renal phosphate wasting disorders. J Clin Invest. 2016;126:667-80 pubmed publisher
    ..Specifically, we evaluated Cyp24 deficiency in Hyp mice, the murine homolog of X-linked dominant hypophosphatemic rickets, and transgenic mice that overexpress a ..
  55. Onishi T, Okawa R, Ogawa T, Shintani S, Ooshima T. Phex mutation causes the reduction of npt2b mRNA in teeth. J Dent Res. 2007;86:158-62 pubmed
    ..We investigated whether a mutation of Phex (phosphate regulating gene homologies to endopeptidase on the X chromosome) has an effect on the expression level ..
  56. Econs M, Barker D, Speer M, Pericak Vance M, Fain P, Drezner M. Multilocus mapping of the X-linked hypophosphatemic rickets gene. J Clin Endocrinol Metab. 1992;75:201-6 pubmed
    X-linked hypophosphatemic rickets (HYP), the most common form of familial hypophosphatemic (vitamin D-resistant) rickets, is an X-linked dominant disorder characterized by decreased renal tubular phosphate reabsorption and consequent ..
  57. Roy S, Tenenhouse H. Transcriptional regulation and renal localization of 1,25-dihydroxyvitamin D3-24-hydroxylase gene expression: effects of the Hyp mutation and 1,25-dihydroxyvitamin D3. Endocrinology. 1996;137:2938-46 pubmed
    X-Linked hypophosphatemic (HYP) mice respond to low phosphate (Pi) intake with a fall in the serum concentration of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and an increase in the renal activity of 1,25-(OH)2D3-24-hydroxylase (24-..
  58. Tenenhouse H, Gauthier C, Martel J, Hoenderop J, Hartog A, Meyer M, et al. Na/P(i) cotransporter ( Npt2) gene disruption increases duodenal calcium absorption and expression of epithelial calcium channels 1 and 2. Pflugers Arch. 2002;444:670-6 pubmed
    ..both duodenal Ca absorption and ECaC1 and ECaC2 mRNA abundance were lower in mice with X-linked hypophosphataemia ( Hyp) than in normal littermates...
  59. Liu S, Brown T, Zhou J, Xiao Z, Awad H, Guilak F, et al. Role of matrix extracellular phosphoglycoprotein in the pathogenesis of X-linked hypophosphatemia. J Am Soc Nephrol. 2005;16:1645-53 pubmed
    ..skeletal mineralization, and aberrant regulation of 1, 25(OH)(2)D(3), is caused by inactivating mutations of Phex, which results in the accumulation of putative phosphaturic factors, called phosphatonins...
  60. Hayashibara T, Hiraga T, Sugita A, Wang L, Hata K, Ooshima T, et al. Regulation of osteoclast differentiation and function by phosphate: potential role of osteoclasts in the skeletal abnormalities in hypophosphatemic conditions. J Bone Miner Res. 2007;22:1743-51 pubmed
    Mice fed with a low Pi diet exhibited decreased osteoclast number. Hyp mice also showed decreased osteoclasts, and high Pi reversed it. Low Pi reduced osteoclast formation and bone resorption in vitro...
  61. Scriver C, Tenenhouse H. Conserved loci on the X chromosome confer phosphate homeostasis in mice and humans. Genet Res. 1990;56:141-52 pubmed
    ..The major form of inherited hypophosphatemia in humans involves an X-linked locus (HPDR, Xp22.31-p21.3)...
  62. Liu S, Guo R, Quarles L. Cloning and characterization of the proximal murine Phex promoter. Endocrinology. 2001;142:3987-95 pubmed
    b>Phex is an endopetidase that regulates systemic phosphate homeostasis...
  63. Collins J, Ghishan F. Molecular cloning, functional expression, tissue distribution, and in situ hybridization of the renal sodium phosphate (Na+/P(i)) transporter in the control and hypophosphatemic mouse. FASEB J. 1994;8:862-8 pubmed
    ..sodium phosphate (Na+/P(i)) transporter and to determine mRNA levels encoding this transporter in control and (Hyp) mice. A 2...
  64. Meyer R, Meyer M, Morgan P. Effects of altered diet on serum levels of 1,25-dihydroxyvitamin D and parathyroid hormone in X-linked hypophosphatemic (Hyp and Gy) mice. Bone. 1996;18:23-8 pubmed
    ..In mice, two different mutations (Hyp and Gy), occurring at separate but closely linked loci, have been proposed as models for this disease...
  65. Karunaratne A, Davis G, Hiller J, Esapa C, Terrill N, Brown S, et al. Hypophosphatemic rickets is associated with disruption of mineral orientation at the nanoscale in the flat scapula bones of rachitic mice with development. Bone. 2012;51:553-62 pubmed publisher
  66. Carpenter T, Moltz K, Ellis B, Andreoli M, McCarthy T, Centrella M, et al. Osteocalcin production in primary osteoblast cultures derived from normal and Hyp mice. Endocrinology. 1998;139:35-43 pubmed
    Rickets and osteomalacia are characteristic features of the Hyp mouse model of human X-linked hypophosphatemia. Hyp mice demonstrate elevated circulating osteocalcin levels, as well as altered regulation of osteocalcin by 1,25(OH)2D3...
  67. Chu E, Fong H, Blethen F, Tompkins K, Foster B, Yeh K, et al. Ablation of systemic phosphate-regulating gene fibroblast growth factor 23 (Fgf23) compromises the dentoalveolar complex. Anat Rec (Hoboken). 2010;293:1214-26 pubmed publisher
    ..Unlike X-linked hypophosphatemic (Hyp) and wild-type (WT) specimens, numerous apoptotic osteocytes and osteoblasts were detected in Fgf23(-/-) specimens...
  68. Seitz S, Barvencik F, Gebauer M, Albers J, Schulze J, Streichert T, et al. Preproenkephalin (Penk) is expressed in differentiated osteoblasts, and its deletion in Hyp mice partially rescues their bone mineralization defect. Calcif Tissue Int. 2010;86:282-93 pubmed publisher
    ..For instance, while there is hallmark evidence for the importance of the endopeptidase Phex, whose inactivation in Hyp mice or human patients causes X-linked hypophosphatemic rickets, it is still largely ..
  69. Carpenter T, Gundberg C. Osteocalcin abnormalities in Hyp mice reflect altered genetic expression and are not due to altered clearance, affinity for mineral, or ambient phosphorus levels. Endocrinology. 1996;137:5213-9 pubmed
    The Hyp mouse manifests rickets and renal wasting of phosphorus. We previously reported elevated circulating osteocalcin in Hyp mice, and a paradoxical decrease in response to 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]...
  70. Wang X, Ikeguchi Y, McCloskey D, Nelson P, Pegg A. Spermine synthesis is required for normal viability, growth, and fertility in the mouse. J Biol Chem. 2004;279:51370-5 pubmed
    ..since this chromosomal deletion extends well beyond the SpmS gene and includes at least one other gene termed Phex. We have bred the Gy carrier female mice with transgenic mice (CAG/SpmS mice) that express spermine synthase from ..
  71. Collins J, Ghishan F. The molecular defect in the renal sodium-phosphate transporter expression pathway of Gyro (Gy) mice is distinct from that of hypophosphatemic (Hyp) mice. FASEB J. 1996;10:751-9 pubmed
    Two animal models of the human disorder hypophosphatemic vitamin D-resistant rickets exist, the Hyp and Gy mice...
  72. Karunaratne A, Boyde A, Esapa C, Hiller J, Terrill N, Brown S, et al. Symmetrically reduced stiffness and increased extensibility in compression and tension at the mineralized fibrillar level in rachitic bone. Bone. 2013;52:689-98 pubmed publisher
    ..Our results indicate that incompletely mineralized fibrils in Hpr mice have greater deformability and lower moduli in both compression and tension, and those compressive and tensile zones have similar moduli at the fibrillar level. ..
  73. Gundberg C, Clough M, Carpenter T. Development and validation of a radioimmunoassay for mouse osteocalcin: paradoxical response in the Hyp mouse. Endocrinology. 1992;130:1909-15 pubmed
    The hypophosphatemic (Hyp) mouse is a model for human familial hypophosphatemic rickets...
  74. Nakagawa N, Ghishan F. Low phosphate diet upregulates the renal and intestinal sodium-dependent phosphate transporter in vitamin D-resistant hypophosphatemic mice. Proc Soc Exp Biol Med. 1994;205:162-7 pubmed
    ..The defect in Na(+)-dependent phosphate transporter has been localized to the kidney of the Hyp mice; however, the adaptation to low-P(i) diet in both kidney and jejunum of the Hyp mice has not been well ..
  75. Andrukhova O, Slavic S, Smorodchenko A, Zeitz U, Shalhoub V, Lanske B, et al. FGF23 regulates renal sodium handling and blood pressure. EMBO Mol Med. 2014;6:744-59 pubmed publisher
    ..by injection of wild-type mice with recombinant FGF23 or by elevated circulating levels of endogenous Fgf23 in Hyp mice increases distal tubular Na(+) uptake and membrane abundance of NCC, leading to volume expansion, hypertension,..
  76. Capparelli A, Roh D, Dhiman J, Jo O, Yanagawa N. Altered proximal tubule glucose metabolism in X-linked hypophosphatemic mice. Endocrinology. 1992;130:328-34 pubmed
    In the present study we examined renal proximal tubule glucose metabolism in the X-linked hypophosphatemic (Hyp/Y) mouse...
  77. Roy S, Martel J, Tenenhouse H. Growth hormone normalizes renal 1,25-dihydroxyvitamin D3-24-hydroxylase gene expression but not Na+-phosphate cotransporter (Npt2) mRNA in phosphate-deprived Hyp mice. J Bone Miner Res. 1997;12:1672-80 pubmed
    The murine X-linked Hyp mutation is characterized by decreased renal expression of type II Na+-phosphate (Pi) cotransporter (Npt2) mRNA and an abnormal vitamin D response to Pi deprivation...
  78. Tenenhouse H, Martel J, Gauthier C, Segawa H, Miyamoto K. Differential effects of Npt2a gene ablation and X-linked Hyp mutation on renal expression of Npt2c. Am J Physiol Renal Physiol. 2003;285:F1271-8 pubmed
    ..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, ..
  79. Qiu Z, Travers R, Rauch F, Glorieux F, Scriver C, Tenenhouse H. Effect of gene dose and parental origin on bone histomorphometry in X-linked Hyp mice. Bone. 2004;34:134-9 pubmed
    X-linked hypophosphatemia (XLH) is characterized by rickets and osteomalacia and arises from mutations in the Phex and PHEX genes in mice (Hyp) and humans, respectively...
  80. Marks K, Kilav R, Berman E, Naveh Many T, Silver J. Parathyroid hormone gene expression in Hyp mice fed a low-phosphate diet. Nephrol Dial Transplant. 1997;12:1581-5 pubmed
    The murine analogue of X-linked hypophosphataemia is the Hyp mouse; it has chronic phosphate depletion from an inherited defect of renal tubular reabsorption...
  81. Bai X, Miao D, Panda D, Grady S, McKee M, Goltzman D, et al. Partial rescue of the Hyp phenotype by osteoblast-targeted PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) expression. Mol Endocrinol. 2002;16:2913-25 pubmed
    Inactivating mutations and/or deletions of PHEX/Phex (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) are responsible for X-linked hypophosphatemic rickets in humans and in the murine homolog Hyp...