DMP1 C-terminal mutant mice recapture the human ARHR tooth phenotype.

[dentinogenesis imperfecta]

DMP 1 mutations in autosomal recessive hypophosphatemic rickets (ARHR ) patients and mice lacking Dmp 1 display an overlapping pathophysiology , such as hypophosphatemia . However , subtle differences exist between the mouse model and human ARHR patients . These differences could be due to a species specificity of human versus mouse , or it may be that the mutant DMP 1 in humans maintains partial function of DMP 1 . In this study we report a deformed tooth phenotype in a human DMP 1 deletion mutation case . Unexpectedly , the deletion of nucleotides 1484 to 1490 (c .1484 _1490 delCTATCAC , delMut , resulting in replacement of the last 18 residues with 33 random amino acids ) showed a severe dentin and enamel defect similar to a dentinogenesis imperfecta (DI ) III -like phenotype . To address the molecular mechanism behind this phenotype , we generated delMut transgenic mice with the endogenous Dmp 1 gene removed . These mutant mice did not recapture the abnormal phenotype observed in the human patient but displayed a mild rachitic tooth phenotype in comparison with that in the Dmp 1 -null mice , suggesting that the DI III -like phenotype may be due to an as -yet-undetermined acquired gene modifier . The mechanism studies showed that the mutant fragment maintains partial function of DMP 1 such as stimulating MAP kinase signaling in vitro . Last , the in vitro and in vivo data support a role of odontoblasts in the control of fibroblast growth factor 23 (FGF-23 ) regulation during early postnatal development , although this regulation on Pi homeostasis is likely limited .

Diseases
Validation

Diseases presenting "hypophosphatemia" symptom

dentinogenesis imperfecta

familial hypocalciuric hypercalcemia

This symptom has already been validated