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A novel Phex mutation with defective glycosylation causes hypophosphatemia and rickets in mice.
J Biomed Sci. 2008 Jan; 15(1):47-59.JB

Abstract

N-ethyl-N-nitrosourea (ENU) mutagenesis is a phenotype-driven approach with potential to assign function to every locus in the mouse genome. In this article, we describe a new mutation, Pug, as a mouse model for X-linked hypophosphatemic rickets (XLH) in human. Mice carrying the Pug mutation exhibit abnormal phenotypes including growth retardation, hypophosphatemia and decreased bone mineral density (BMD). The new mutation was mapped to X-chromosome between 65.4 cM and 66.6 cM, where Phex gene resides. Sequence analysis revealed a unique T-to-C transition mutation resulting in Phe-to-Ser substitution at amino acid 80 of PHEX protein. In vitro studies of Pug mutation demonstrated that PHEX(pug) was incompletely glycosylated and sequestrated in the endoplasmic reticulum region of cell, whereas wild-type PHEX could be fully glycosylated and transported to the plasma membrane to exert its function as an endopeptidase. Taken together, the Pug mutant directly confirms the role of Phex in phosphate homeostasis and normal skeletal development and may serves as a new disease model of human hypophosphatemic rickets.

Authors+Show Affiliations

Model Animal Research Center, Nanjing University, 12 Xuefu Road, Pukou District, Nanjing, 210061, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17710565

Citation

Xiong, Xiwen, et al. "A Novel Phex Mutation With Defective Glycosylation Causes Hypophosphatemia and Rickets in Mice." Journal of Biomedical Science, vol. 15, no. 1, 2008, pp. 47-59.
Xiong X, Qi X, Ge X, et al. A novel Phex mutation with defective glycosylation causes hypophosphatemia and rickets in mice. J Biomed Sci. 2008;15(1):47-59.
Xiong, X., Qi, X., Ge, X., Gu, P., Zhao, J., Zhao, Q., & Gao, X. (2008). A novel Phex mutation with defective glycosylation causes hypophosphatemia and rickets in mice. Journal of Biomedical Science, 15(1), 47-59.
Xiong X, et al. A Novel Phex Mutation With Defective Glycosylation Causes Hypophosphatemia and Rickets in Mice. J Biomed Sci. 2008;15(1):47-59. PubMed PMID: 17710565.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel Phex mutation with defective glycosylation causes hypophosphatemia and rickets in mice. AU - Xiong,Xiwen, AU - Qi,Xin, AU - Ge,Xiaomei, AU - Gu,Pengyu, AU - Zhao,Jing, AU - Zhao,Qingshun, AU - Gao,Xiang, Y1 - 2007/08/21/ PY - 2007/04/23/received PY - 2007/07/21/accepted PY - 2007/8/22/pubmed PY - 2008/2/28/medline PY - 2007/8/22/entrez SP - 47 EP - 59 JF - Journal of biomedical science JO - J Biomed Sci VL - 15 IS - 1 N2 - N-ethyl-N-nitrosourea (ENU) mutagenesis is a phenotype-driven approach with potential to assign function to every locus in the mouse genome. In this article, we describe a new mutation, Pug, as a mouse model for X-linked hypophosphatemic rickets (XLH) in human. Mice carrying the Pug mutation exhibit abnormal phenotypes including growth retardation, hypophosphatemia and decreased bone mineral density (BMD). The new mutation was mapped to X-chromosome between 65.4 cM and 66.6 cM, where Phex gene resides. Sequence analysis revealed a unique T-to-C transition mutation resulting in Phe-to-Ser substitution at amino acid 80 of PHEX protein. In vitro studies of Pug mutation demonstrated that PHEX(pug) was incompletely glycosylated and sequestrated in the endoplasmic reticulum region of cell, whereas wild-type PHEX could be fully glycosylated and transported to the plasma membrane to exert its function as an endopeptidase. Taken together, the Pug mutant directly confirms the role of Phex in phosphate homeostasis and normal skeletal development and may serves as a new disease model of human hypophosphatemic rickets. SN - 1021-7770 UR - https://www.unboundmedicine.com/medline/citation/17710565/A_novel_Phex_mutation_with_defective_glycosylation_causes_hypophosphatemia_and_rickets_in_mice_ L2 - https://dx.doi.org/10.1007/s11373-007-9199-6 DB - PRIME DP - Unbound Medicine ER -