title: Ectopic mineralization of connective tissue in Abcc6-/- mice: effects of dietary modifications and a phosphate binder--a preliminary study.
abstract: Pseudoxanthoma elasticum (PXE), a heritable multisystem disorder, is caused by mutations in the ABCC6 gene. We have developed a murine model for PXE by targeted inactivation of the corresponding mouse gene. A feature of this mouse model is ectopic mineralization of connective tissue capsule surrounding the bulb of vibrissae. This study was designed to investigate the effect of dietary sevelamer hydrochloride (Renagel), a phosphate binder, and specific mineral modifications on ectopic mineralization of connective tissue in Abcc6-/- mice. Three groups were fed a specific diet: (i) a standard rodent diet, (ii) a standard rodent diet supplemented with sevelamer hydrochloride, and (iii) a custom experimental diet with specific mineral modifications (high phosphorus, low calcium and low magnesium). The degree of mineralization was determined in hematoxylin-eosin-stained sections using computerized morphometric analysis and by chemical assays to measure the calcium and phosphorus content of the vibrissae. The results indicated increased mineralization in the Abcc6-/- mice fed a standard diet or a diet with mineral modifications as compared with control mice fed a standard diet. However, feeding Abcc6-/- mice with diet supplemented with sevelamer hydrochloride did not improve mineralization, in comparison to mice fed with normal diet. Collectively, these results suggest that the mineralization process in PXE may be exacerbated by changes in mineral intake. The role of dietary minerals, and phosphorus in particular, as well as that of phosphate binders, in ectopic mineralization of PXE, merits further investigation.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: LaRusso
authors.forename: Qiujie
authors.initials: Q
authors.lastname: Jiang
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D002114:Calcinosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002130:Calcium Phosphates / Q000032:analysis; D002614:Chelating Agents / Q000627:therapeutic use*; D003238:Connective Tissue / Q000473:pathology; D004195:Disease Models, Animal; D005247:Feeding Behavior; D007091:Image Processing, Computer-Assisted; D007668:Kidney / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008853:Microscopy; D008903:Minerals / Q000032:analysis; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009206:Myocardium / Q000473:pathology; D011073:Polyamines / Q000627:therapeutic use*; D011561:Pseudoxanthoma Elasticum / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000069603:Sevelamer; D014738:Vibrissae / Q000737:chemistry / Q000473:pathology
chemical_list: D018528:ATP-Binding Cassette Transporters; D002130:Calcium Phosphates; D002614:Chelating Agents; D008903:Minerals; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011073:Polyamines; D000069603:Sevelamer; C504743:Abcc6 protein, mouse; C020243:calcium phosphate