弹性假黄瘤
生物
结缔组织
Von Kossa染色
病理
矿化(土壤科学)
异位钙化
钙化
内分泌学
医学
碱性磷酸酶
遗传学
生态学
生物化学
土壤水分
酶
作者
John F. Klement,Yasushi Matsuzaki,Jiang Qiu,Joseph Terlizzi,Hae Young Choi,Norihiro Fujimoto,Kehua Li,Leena Pulkkinen,David E. Birk,John P. Sundberg,Jouni Uitto
标识
DOI:10.1128/mcb.25.18.8299-8310.2005
摘要
Pseudoxanthoma elasticum (PXE), characterized by connective tissue mineralization of the skin, eyes, and cardiovascular system, is caused by mutations in the ABCC6 gene.ABCC6 encodes multidrug resistanceassociated protein 6 (MRP6), which is expressed primarily in the liver and kidneys.Mechanisms producing ectopic mineralization as a result of these mutations remain unclear.To elucidate this complex disease, a transgenic mouse was generated by targeted ablation of the mouse Abcc6 gene.Abcc6 null mice were negative for Mrp6 expression in the liver, and complete necropsies revealed profound mineralization of several tissues, including skin, arterial blood vessels, and retina, while heterozygous animals were indistinguishable from the wild-type mice.Particularly striking was the mineralization of vibrissae, as confirmed by von Kossa and alizarin red stains.Electron microscopy revealed mineralization affecting both elastic structures and collagen fibers.Mineralization of vibrissae was noted as early as 5 weeks of age and was progressive with age in Abcc6 ؊/؊ mice but was not observed in Abcc6 ؉/؊ or Abcc6 ؉/؉ mice up to 2 years of age.A total body computerized tomography scan of Abcc6 ؊/؊ mice revealed mineralization in skin and subcutaneous tissue as well as in the kidneys.These data demonstrate aberrant mineralization of soft tissues in PXE-affected organs, and, consequently, these mice recapitulate features of this complex disease.
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