title: Elevated dietary magnesium prevents connective tissue mineralization in a mouse model of pseudoxanthoma elasticum (Abcc6(-/-)).
abstract: Pseudoxanthoma elasticum (PXE) is an autosomal recessive multisystem disorder characterized by ectopic connective tissue mineralization, with clinical manifestations primarily in the skin, eyes, and cardiovascular system. There is considerable, both intra- and interfamilial, variability in the spectrum of phenotypic presentation. Previous studies have suggested that mineral content of the diet may modify the severity of the clinical phenotype in PXE. In this study, we utilized a targeted mutant mouse (Abcc6(-/-)) as a model system for PXE. We examined the effects of changes in dietary phosphate and magnesium on the mineralization process using calcification of the connective tissue capsule surrounding the vibrissae as an early phenotypic biomarker. Mice placed on custom-designed diets either high or low in phosphate did not show changes in mineralization, which was similar to that noted in Abcc6(-/-) mice on control diet. However, mice placed on diet enriched in magnesium (fivefold) showed no evidence of connective tissue mineralization in this mouse model of PXE. The inhibitory capacity of magnesium was confirmed in a cell-based mineralization assay system in vitro. Collectively, our observations suggest that assessment of dietary magnesium in patients with PXE may be warranted.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: LaRusso
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.forename: Qiujie
authors.initials: Q
authors.lastname: Jiang
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000502:physiology*; D053180:Animal Nutrition Sciences; D000818:Animals; D001011:Aorta / Q000378:metabolism; D003238:Connective Tissue / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D008274:Magnesium / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009130:Muscle, Smooth / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism; D011561:Pseudoxanthoma Elasticum / Q000235:genetics* / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D008274:Magnesium; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010281:Parathyroid Hormone; D010710:Phosphates; D010758:Phosphorus; C504743:Abcc6 protein, mouse