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- Title
Inherited Junctional Epidermolysis Bullosa in the German Pointer: Establishment of a Large Animal Model.
- Authors
Capt, Annabelle; Spirito, Flavia; Guaguere, Eric; Spadafora, Anne; Ortonne, Jean-Paul; Meneguzzi, Guerrino
- Abstract
Junctional epidermolysis bullosa (JEB) is a genodermatosis suitable for gene therapy because conventional treatments are ineffective. Here, we elucidate the genetic basis of mild JEB in a breed of dogs that display all the clinical traits observed in JEB patients. The condition is associated with reduced expression of laminin 5 caused by a homozygous insertion (4818+207ins6.5 kb) of repetitive satellite DNA within intron 35 of the gene (lama3) for the lamininα3 chain. The intronic mutation interferes with maturation of theα3 pre-messenger RNA resulting in the coexpression of a transcript with a 227 nucleotide insertion and a wild-type mRNA that encodes scant amounts of theα3 polypeptide. Our results show that the amino acid sequence and structure of the canine and humanα3 chain are highly conserved and that the reduced expression of laminin 5 affects the adhesion and clonogenic potential of the JEB keratinocytes. These JEB dogs provide the opportunity to perform gene delivery in a naturally occurring genodermatosis and to evaluate host tolerance to recombinant laminin 5.
- Subjects
EPIDERMOLYSIS bullosa; MESSENGER RNA; AMINO acid sequence; KERATINOCYTES; PEPTIDE hormones; GENE therapy
- Publication
Journal of Investigative Dermatology, 2005, Vol 124, Issue 3, p530
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/j.0022-202X.2004.23584.x