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Mammalian Genome

, Volume 8, Issue 9, pp 673–681 | Cite as

IAP insertion in the murine LamB3 gene results in junctional epidermolysis bullosa

  • Joan E. Kuster
  • Mary H. Guarnieri
  • Jeffrey G. Ault
  • Lorraine Flaherty
  • Pamela J. Swiatek
Original Contribution

Abstract

The laminin-5 molecule functions in the attachment of various epithelia to basement membranes. Mutations in the laminin-5-coding genes have been associated with Herlitz junctional epidermolysis bullosa (HJEB), a severe and often lethal blistering disease of humans. Here we report the characterization of a spontaneous mouse mutant with an autosomal recessive blistering disease. These mice exhibit sub-epithelial blisters of the skin and mucosal surfaces and abnormal hemidesmosomes lacking subbasal dense plates. By linkage analysis the genetic defect was localized to a 2-cM region on distal Chromosome (Chr) 1 where a laminin-5 subunit gene, LamB3, was previously localized. LamB3 mRNA and laminin-5 protein were undetectable by Northern blot analysis and immunohistochemical methods, respectively. DNA sequence analysis indicated that the LamB3 genetic defect resulted from disruption of the coding sequence by insertion of an intracisternal-A particle (IAP) at an exon/intron junction. These findings suggest a role for laminin-5 in hemidesmosome formation and indicate that the LamB3IAP mutant is a useful mouse model for HJEB.

Keywords

Integrin Epidermolysis Bullosa Basement Membrane Zone Tissue Separation Junctional Epidermolysis Bullosa 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • Joan E. Kuster
    • 1
  • Mary H. Guarnieri
    • 1
  • Jeffrey G. Ault
    • 2
  • Lorraine Flaherty
    • 1
  • Pamela J. Swiatek
    • 1
  1. 1.Division of Genetic Disorders, Laboratory of Developmental GeneticsWadsworth Center, New York State Department of HealthAlbanyUSA
  2. 2.Division of Molecular MedicineLaboratory of Structural PathologyAlbanyUSA

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