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An Ethyl-Nitrosourea-Induced Point Mutation in Phex causes exon skipping, X-linked Hypophosphatemia, and Rickets

Citation

Carpinelli, M and Wicks, I and Sims, NA and O'Donnell, K and Hanzinikolas, K and Burt, R and Foote, SJ and Bahlo, M and Alexander, WS and Hilton, DJ, An Ethyl-Nitrosourea-Induced Point Mutation in Phex causes exon skipping, X-linked Hypophosphatemia, and Rickets, American Journal of Pathology, 161, (5) pp. 1925-1933. ISSN 0002-9440 (2002) [Refereed Article]

DOI: doi:10.1016/S0002-9440(10)64468-9

Abstract

We describe the clinical, genetic, biochemical, and molecular characterization of a mouse that arose in the ftrst generation (G 1 ) of a random mutagenesis screen with the chemical mutagen ethyl-nitrosourea. The mouse was observed to have skeletal abnormalities inherited with an X-linked dominant pattern of inheritance. The causative mutation, named Skeletal abnormality 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. This point mutation caused skipping of exon 8 from Phex mRNA, hypophosphatemia, and features of rickets. This experimentally induced phenotype mirrors the human condition X-linked hypophosphatemia; directly confirms the role of Phex in phosphate homeostasis, normal skeletal development, and rickets; and illustrates the power of mutagenesis in exploring animal models of human disease. © 2002 Elsevier Science Ltd. All rights reserved.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Medical Genetics (excl. Cancer Genetics)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Skeletal System and Disorders (incl. Arthritis)
Author:Foote, SJ (Professor Simon Foote)
ID Code:35059
Year Published:2002
Web of Science® Times Cited:28
Deposited By:Menzies Centre
Deposited On:2005-08-01
Last Modified:2005-08-02
Downloads:0

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