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PMID: 9271670 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Mammalian genome : official journal of the International Mammalian Genome Society ·Vol. 8 ·No. 9 ·1997-09-00 ·Pages 673-81

Kuster JE, Guarnieri MH, Ault JG, Flaherty L, Swiatek PJ

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 sub-basal 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 LamB3(IAP) mutant is a useful mouse model for HJEB.

MeSH Terms
Animals Blotting, Northern Cell Adhesion Molecules/genetics,metabolism Chromosome Mapping DNA Transposable Elements Disease Models, Animal Epidermolysis Bullosa, Junctional/genetics Female Gene Expression Regulation, Developmental Male Mice Mice, Inbred C3H Mice, Inbred Strains Mutation Phenotype Polymerase Chain Reaction Skin/pathology,ultrastructure Skin Diseases/genetics,pathology
Chemicals
Cell Adhesion Molecules DNA Transposable Elements kalinin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kuster J E
Division of Genetic Disorders, Laboratory of Developmental Genetics, Wadsworth Center, New York State Department of Health, P.O. Box 22002, Albany, New York 12201-2002, USA.
Guarnieri M H
Ault J G
Flaherty L
Swiatek P J
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Article Info
Journal
Mammalian genome : official journal of the International Mammalian Genome Society
Abbr.
Mamm Genome
ISSN
0938-8990
DOI
10.1007/s003359900535
Published
1997-09-00
Pages
673-81
Language
English
Region
United States
NLM ID
9100916
Subset
IM
Grants
NIGMS NIH HHS · GM50283 · United States
External Links
PubMed source DOI: 10.1007/s003359900535 View journal details
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