An ethyl-nitrosourea-induced point mutation in Phex causes exon skipping, X-linked hypophosphatemia, and rickets
- Carpinelli, MR; Wicks, IP; Sims, NA; O'Donnell, K; Hanzinikolas, K; Burt, R; Foote, SJ; Bahlo, M; Alexander, WS; Hilton, DJ;
Publication Year 2002-11, Volume 161, Issue #5, Page 1925-1933
- Journal Title
- AMERICAN JOURNAL OF PATHOLOGY
- Publication Type
- Journal Article
- We describe the clinical, genetic, biochemical, and molecular characterization of a mouse that arose in the first generation (G,) 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.
- AMER SOC INVESTIGATIVE PATHOLOGY, INC
- PEX GENE; HYP MUTATION; MOUSE; OSTEOMALACIA; MUTAGENESIS; FGF23
- Publisher's Version
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Creation Date: 2002-11-01 12:00:00Last Modified: 0001-01-01 12:00:00