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

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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.

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Authors and Affiliations

  1. Division of Genetic Disorders, Laboratory of Developmental Genetics, Wadsworth Center, New York State Department of Health, P.O. Box 22002, 12201-2002, Albany, New York, USA

    Joan E. Kuster, Mary H. Guarnieri, Lorraine Flaherty & Pamela J. Swiatek

  2. Division of Molecular Medicine, Laboratory of Structural Pathology, Wadsworth Center, New York State Department of Health, P.O. Box 22002, 12201-2002, Albany, New York, USA

    Jeffrey G. Ault

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  1. Joan E. Kuster
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  2. Mary H. Guarnieri
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  3. Jeffrey G. Ault
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  4. Lorraine Flaherty
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Kuster, J.E., Guarnieri, M.H., Ault, J.G. et al. IAP insertion in the murine LamB3 gene results in junctional epidermolysis bullosa. Mammalian Genome 8, 673–681 (1997). https://doi.org/10.1007/s003359900535

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