title: Variable patterns of ectopic mineralization in Enpp1asj-2J mice, a model for generalized arterial calcification of infancy.
abstract: Generalized arterial calcification of infancy (GACI) is an autosomal recessive disorder characterized by early onset of extensive mineralization of the cardiovascular system. The classical forms of GACI are caused by mutations in the ENPP1 gene, encoding a membrane-bound pyrophosphatase/phosphodiesterase that hydrolyzes ATP to AMP and inorganic pyrophosphate. The asj-2J mouse harboring a spontaneous mutation in the Enpp1 gene has been characterized as a model for GACI. These mutant mice develop ectopic mineralization in skin and vascular connective tissues as well as in cartilage and collagen-rich tendons and ligaments. This study examined in detail the temporal ectopic mineralization phenotype of connective tissues in this mouse model, utilizing a novel cryo-histological method that does not require decalcification of bones. The wild type, heterozygous, and homozygous mice were administered fluorescent mineralization labels at 4 weeks (calcein), 10 weeks (alizarin complexone), and 11 weeks of age (demeclocycline). Twenty-four hours later, outer ears, muzzle skin, trachea, aorta, shoulders, and vertebrae were collected from these mice and examined for progression of mineralization. The results revealed differential timeline for disease initiation and progression in various tissues of this mouse model. It also highlights the advantages of cryo-histological fluorescent imaging technique to study mineral deposition in mouse models of ectopic mineralization disorders.
authors.affiliation: Department of Dermatology and Cutaneous Biology, The Sidney Kimmel Medical College and The PXE International Center of Excellence in Research and Clinical Care, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Sarah Y
authors.initials: SY
authors.lastname: Siu
authors.affiliation: Center for Regenerative Medicine and Skeletal Development, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Nathaniel A
authors.initials: NA
authors.lastname: Dyment
authors.affiliation: Center for Regenerative Medicine and Skeletal Development, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Rowe
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Sundberg
authors.affiliation: Department of Dermatology and Cutaneous Biology, The Sidney Kimmel Medical College and The PXE International Center of Excellence in Research and Clinical Care, Thomas Jefferson University, Philadelphia, PA, USA.|Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
authors.affiliation: Department of Dermatology and Cutaneous Biology, The Sidney Kimmel Medical College and The PXE International Center of Excellence in Research and Clinical Care, Thomas Jefferson University, Philadelphia, PA, USA.|Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Qiaoli
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage; D003238:Connective Tissue / Q000201:enzymology / Q000473:pathology*; D003707:Demeclocycline / Q000008:administration & dosage; D018450:Disease Progression; D005452:Fluoresceins / Q000008:administration & dosage; D005456:Fluorescent Dyes / Q000008:administration & dosage; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008856:Microscopy, Fluorescence / Q000379:methods; D009154:Mutation; D010641:Phenotype; D010727:Phosphoric Diester Hydrolases / Q000235:genetics* / Q000378:metabolism; D011755:Pyrophosphatases / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D061205:Vascular Calcification / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*
chemical_list: D000880:Anthraquinones; D005452:Fluoresceins; D005456:Fluorescent Dyes; C070804:alizarin complexone; D003707:Demeclocycline; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases; C007740:fluorexon
keywords: Pathology Section; cryohistology; ectopic mineralization; generalized arterial calcification of infancy; mouse models