title: Animal models of pathologic calcification.
abstract: Recent progress in genetics and mouse genomics enables researchers to unveil the molecular basis for mouse phenotypes that express pathologic calcification in soft tissue and/or articular tissues. A newly identified multipass transmembrane protein, ANK, appears to function as an inorganic pyrophosphate (PPi) transporter or regulator of PPi transport. Abnormal extracellular PPi (ePPi) metabolism has been implicated in abnormal calcification, decreased concentrations predisposing to basic calcium phosphate (BCP) deposition, and increased concentrations promoting calcium pyrophosphate dihydrate (CPPD) crystal deposition in articular tissues. The chromosomal location of human ANK overlaps the locus identified in several kindreds affected with familial chondrocalcinosis. Deficient generation of ePPi by the ectoenzyme nucleoside triphosphate pyrophosphohydrolase also results in excessive ossification and ectopic deposition of BCP crystals in tiptoe-walking mice and PC-1 null mice. Recent studies reinforce the important regulatory role of ePPi in pathologic and physiologic calcification.
authors: Division of Rheumatology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. imasuda@mcw.edu
authors: Ikuko
authors: I
authors: Masuda
authors: Jun
authors: J
authors: Hirose
mesh_terms: D000818:Animals; D002114:Calcinosis / Q000209:etiology* / Q000235:genetics*; D011756:Diphosphates / Q000378:metabolism; D004195:Disease Models, Animal; D006706:Homeostasis; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D028061:Phosphate Transport Proteins; D011755:Pyrophosphatases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C498770:ANKH protein, human; D011756:Diphosphates; D008565:Membrane Proteins; D028061:Phosphate Transport Proteins; D016212:Transforming Growth Factor beta; C410982:ank protein, mouse; D011755:Pyrophosphatases; C021895:nucleoside triphosphate pyrophosphatase