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 Type:	Refereed Article
Research Division:	Biomedical and Clinical Sciences
Research Group:	Clinical sciences
Research Field:	Medical genetics (excl. cancer genetics)
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Foote, SJ (Professor Simon Foote)
ID Code:	35059
Year Published:	2002
Web of Science® Times Cited:	32
Deposited By:	Menzies Centre
Deposited On:	2005-08-01
Last Modified:	2005-08-02
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