A novel Phex mutation in a new mouse model of hypophosphatemic rickets

Journal of Cellular Biochemistry
Celeste OwenJane E Aubin

Abstract

X-linked hypophosphatemic rickets (XLH) is a dominantly inherited disease characterized by renal phosphate wasting, aberrant vitamin D metabolism, and defective bone mineralization. It is known that XLH in humans and in certain mouse models is caused by inactivating mutations in PHEX/Phex (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). By a genome-wide N-ethyl-N-nitrosourea (ENU)-induced mutagenesis screen in mice, we identified a dominant mouse mutation that exhibits the classic clinical manifestations of XLH, including growth retardation, skeletal abnormalities (rickets/osteomalacia), hypophosphatemia, and increased serum alkaline phosphatase (ALP) levels. Mapping and sequencing revealed that these mice carry a point mutation in exon 14 of the Phex gene that introduces a stop codon at amino acid 496 of the coding sequence (Phex(Jrt) also published as Phex(K496X) [Ichikawa et al., 2012]). Fgf23 mRNA expression as well as that of osteocalcin, bone sialoprotein, and matrix extracellular phosphoglycoprotein was upregulated in male mutant long bone, but that of sclerostin was unaffected. Although Phex mRNA is expressed in bone from mutant hemizygous male mice (Phex(Jrt)/Y mice), no Phex protein w...Continue Reading

References

Feb 1, 1997·Human Molecular Genetics·T M StromT Meitinger
Apr 1, 1997·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A J Turner, K Tanzawa
Sep 1, 1997·Calcified Tissue International·L RifasL V Avioli
Mar 9, 1999·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·H S Tenenhouse
Jan 5, 2000·Kidney International·M K Drezner
Aug 10, 2000·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·A F RuchonG Boileau
May 10, 2001·Proceedings of the National Academy of Sciences of the United States of America·T ShimadaT Yamashita
Aug 15, 2001·The Journal of Clinical Endocrinology and Metabolism·P T ChristieR V Thakker
Nov 20, 2001·The Journal of Biological Chemistry·Shiguang LiuL Darryl Quarles
Dec 12, 2001·Kidney International·K E WhiteM J Econs
Jan 29, 2002·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·D L ThompsonR Kumar
Nov 5, 2002·The American Journal of Pathology·Marina R CarpinelliDouglas J Hilton
May 3, 2003·The Journal of Clinical Endocrinology and Metabolism·Yves SabbaghHarriet S Tenenhouse
Mar 20, 2004·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Bettina Lorenz-DepiereuxEva M Eicher
Oct 26, 2005·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Sheng Zhao, Russell D Fernald
Feb 2, 2006·American Journal of Physiology. Endocrinology and Metabolism·Shiguang LiuL Darryl Quarles
Aug 22, 2007·Journal of Biomedical Science·Xiwen XiongXiang Gao
Jan 4, 2008·The Journal of Clinical Investigation·Baozhi YuanMarc K Drezner
Feb 20, 2008·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Hua WangNorihiko Maeda
Jul 29, 2008·Current Opinion in Nephrology and Hypertension·Tim M Strom, Harald Jüppner
Feb 12, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Gerald J AtkinsDavid M Findlay
Apr 22, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Aline MartinL Darryl Quarles
Oct 19, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Shoji IchikawaMichael J Econs

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Citations

May 24, 2013·Calcified Tissue International·Shoji IchikawaMichael J Econs
Mar 9, 2013·Frontiers of Medicine·Eryuan Liao
Oct 19, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Shoji IchikawaMichael J Econs
Feb 7, 2015·International Journal of Oral Science·Yu-Chen Guo, Quan Yuan
Jun 14, 2014·Annals of Pediatric Endocrinology & Metabolism·Chong Kun CheonHan-Wook Yoo
Feb 12, 2014·The Journal of Clinical Endocrinology and Metabolism·Telma PalomoFrank Rauch
Jun 15, 2019·FEBS Letters·Ludmilla BärMichael Föller
Feb 28, 2019·Orphanet Journal of Rare Diseases·Signe Sparre Beck-NielsenOuti Mäkitie

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