PHEXMutation IncreasesExpression in a New ENU Mouse Model for XLH Disease.

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 PHEXexpression. Actually,mice show an increase in,, andandmRNA expression similar to those observed inmice. Femoral osteocalcin and sclerostin anddo not show any significant variation inmice. 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 PHEXloss 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.