PHEX Mutation Increases Expression in a New ENU Mouse Model for XLH Disease

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2022 Aug 26

PMID 36011266

Authors

Carole El Hakam

Alexis Parente

Fabienne Baraige

Laetitia Magnol

Lionel Forestier

Florent Di Meo

Veronique Blanquet

Affiliations

Soon will be listed here.

Abstract

mouse is a new ENU mouse model for XLH disease due to Leu to Pro amino acid modification at position 222. mouse is characterized by growth retardation, hypophosphatemia, hypocalcemia, reduced body bone length, and increased epiphyseal growth plate thickness and femur diameter despite the increase in PHEX expression. Actually, mice show an increase in , , and and mRNA expression similar to those observed in mice. Femoral osteocalcin and sclerostin and do not show any significant variation in mice. Molecular dynamics simulations support the experimental data. P222 might locally break the E217-Q224 -sheet, which in turn might disrupt inter--sheet interactions. We can thus expect local protein misfolding, which might be responsible for the experimentally observed PHEX loss of function. This model could be a valuable addition to the existing XLH model for further comprehension of the disease occurrence and testing of new therapies.

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