ABSTRACT Collagen XVII has been identified as having a role in inherited junctional epidermolysis bullosa non-Herlitz (JEB-other, MIM #226650). The role of collagen XVII in both autoimmune and genetic blistering disorders demonstrates its relevance to dermal-epidermal adhesion. Collagen XVII is a major structural component of the hemidesmosome (HD), a highly specialized multiprotein complex that mediates the anchorage of basal epithelial cells to the underlying basement membrane in stratified, pseudostratified, and transitional epithelia. This article examines the genetic and pathological features of collagen XVII.
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Article: The Collagen Family[Show abstract] [Hide abstract]
ABSTRACT: Collagens are the most abundant proteins in mammals. The collagen family comprises 28 members that contain at least one triple-helical domain. Collagens are deposited in the extracellular matrix where most of them form supramolecular assemblies. Four collagens are type II membrane proteins that also exist in a soluble form released from the cell surface by shedding. Collagens play structural roles and contribute to mechanical properties, organization, and shape of tissues. They interact with cells via several receptor families and regulate their proliferation, migration, and differentiation. Some collagens have a restricted tissue distribution and hence specific biological functions.Cold Spring Harbor perspectives in biology 01/2011; 3(1):a004978. DOI:10.1101/cshperspect.a004978 · 8.23 Impact Factor
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ABSTRACT: Heritable skin diseases represent a broad spectrum of clinical manifestations due to mutations in ∼500 different genes. A number of model systems have been developed to advance our understanding of the pathomechanisms of genodermatoses. Zebrafish (Danio rerio), a freshwater vertebrate, has a well-characterized genome, the expression of which can be easily manipulated. The larvae develop rapidly, with all major organs having developed by 5-6 days post-fertilization, including the skin, consisting of the epidermis comprising two cell layers and separated from the dermal collagenous matrix by a basement membrane. This perspective highlights the morphological and ultrastructural features of zebrafish skin, in the context of cutaneous gene expression. These observations suggest that zebrafish provide a useful model system to study the molecular aspects of skin development, as well as the pathogenesis and treatment of select heritable skin diseases.Journal of Investigative Dermatology 03/2011; 131(3):565-71. DOI:10.1038/jid.2010.388 · 6.37 Impact Factor
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ABSTRACT: Junctional epidermolysis bullosa of late onset (JEB-lo) is a rare disease characterized by blistering of primarily the hands and feet starting in childhood. The pathogenesis remains unclear. To clarify the pathogenesis of JEB-lo. Two patients with JEB-lo, a brother and a sister, were examined using electron microscopy (EM), immunofluorescence (IF) antigen mapping and molecular analysis. We found subtle changes in IF antigen mapping and EM. The most remarkable changes were loss of the apical-lateral staining of monoclonal antibodies (mAbs) against type XVII collagen (Col17), and a broadened distribution of mAb staining against the ectodomain of Col17, laminin-332 and type VII collagen. Mutation analysis of COL17A1, encoding Col17, showed a compound heterozygosity for a novel mutation c.1992_1995delGGGT and the known mutation c.3908G>A in both patients. The deletion c.1992_1995delGGGT results in a premature termination codon and mRNA decay, leaving the patients functionally hemizygous for the missense mutation c.3908G>A (p.R1303Q) in the noncollagenous 4 domain of Col17. JEB-lo is an autosomal recessive disorder caused by mutations in COL17A1, and subtle aberrations in EM and IF antigen mapping are clues to diagnosis.British Journal of Dermatology 04/2011; 164(6):1280-4. DOI:10.1111/j.1365-2133.2011.10359.x · 4.10 Impact Factor