ALTERED LAMININ-5 EXPRESSION DUE TO MUTATIONS IN THE GENE ENCODING THE BETA-3 CHAIN (LAMB3) IN GENERALIZED ATROPHIC BENIGN EPIDERMOLYSIS-BULLOSA

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:104

Article

MCGRATH, JA ; PULKKINEN, L ; CHRISTIANO, AM ; LEIGH, IM ; EADY, RAJ ; UITTO, J

关键词: JUNCTIONAL EPIDERMOLYSIS BULLOSA;    KALININ;    NICEIN;   

DOI  :  10.1111/1523-1747.ep12605904

来源: Elsevier

【 摘 要 】

The anchoring filament component laminin 5 (kalinin/nicein) is a candidate protein for mutations in some hereditary blistering skin disorders. In this study, laminin 5 expression was assessed in a family with generalized atrophic benign epidermolysis bullosa, a non-lethal variant of the junctional form of epidermolysis bullosa. Immunofluorescence microscopy of the skin basement-membrane zone with a monoclonal antibody (GB3) revealed reduced antilaminin 5 staining compared to normal controls. The labeling, when examined by immunoelectron microscopy, was present within the lower lamina lucida, immediately below the plane of blister formation. Numerous hemidesmosomes and well-formed anchoring filaments were seen on transmission electron microscopy. Polymerase chain reaction amplification of genomic DNA encoding the beta 3 subunit (LAMB3) of laminin 5, heteroduplex analysis of the polymerase chain reaction products, and nucleotide sequencing of the heteroduplexes revealed two putative mutations within the LAMB3 gene; these consisted of a premature termination codon in exon 3 and a missense mutation in exon 7. Exons 3 and 7 encode part of domain VI of the laminin 5 beta 3 chain short arm. This globular domain of the protein has been postulated to have an important function in the interaction of laminin 5 with other structural components of the basement membrane zone, such as laminin 6 (K-laminin). Thus the mutations delineated in this family may have a critical pathogenetic significance in reducing adhesion between the epidermis and the dermis.

【 授权许可】

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