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Evidence for Phex haploinsufficiency in murine X-linked hypophosphatemia
1Genetics Unit, Shriners Hospital, Departments of Surgery and Human Genetics, McGill University, Montreal, Quebec, Canada H3G 1A6.
Summary
Mutations in the PHEX gene cause X-linked hypophosphatemia (HYP). In mice, a deletion in the Phex gene
Area of Science:
- Genetics
- Molecular Biology
- Biochemistry
Background:
- X-linked hypophosphatemia (HYP) is caused by mutations in the PHEX gene.
- Previous studies characterized the murine Phex cDNA and its expression in bone and teeth.
Purpose of the Study:
- To clone and characterize the 3'UTR of the Phex gene.
- To investigate the genetic basis of HYP in the Hyp mouse model.
Main Methods:
- Cloning of the Phex 3'UTR
- Southern blot analysis
- RT-PCR and Northern blot analyses
- Western blot analysis
Main Results:
- The entire 3.5-kb 3'UTR of the Phex gene was cloned.
- A deletion encompassing exons 16-22 (including the 3' end of the coding sequence and the 3'UTR) was identified in the Hyp mouse model.
- Northern blot analysis showed lack of Phex mRNA expression from the mutant allele in Hyp heterozygotes.
- Phex protein expression was confirmed in heterozygotes.
Conclusions:
- The identified deletion in the Phex gene in Hyp mice leads to Phex haploinsufficiency.
- Phex haploinsufficiency explains the dominant inheritance pattern of HYP in mice.