Dystrophic form of inherited epidermolysis bullosa in a dog (Akita Inu)

Nagata, Masahiko; Shimizu, Hiroshi; Masunaga, Takuji; Nishikawa, Takeji; Nanko, Hiroko; Kariya, Kazuhiro; Washizu, Tsukimi; Ishida, Takuo

doi:10.1111/j.1365-2133.1995.tb06942.x

Cited by 23 publications

(15 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…JEB-like phenotypes have been previously described in dogs (Capt et al , 2005; Dunstan et al , 1988; Nagata et al , 1997; Nagata et al , 1995) and horses (Frame et al , 1988; Spirito et al , 2002). A viable mouse model of JEB would be invaluable, since it can manipulated experimentally and genetically.…”

Section: Introductionmentioning

confidence: 92%

A Mouse Model of Generalized Non-Herlitz Junctional Epidermolysis Bullosa

Bubier

Sproule

Alley

et al. 2010

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Epidermolysis bullosa (EB) is a class of intractable, rare, genetic disorders characterized by fragile skin and blister formation as a result of dermal-epidermal mechanical instability. EB presents with considerable clinical and molecular heterogeneity. Viable animal models of junctional epidermolysis bullosa (JEB), that both mimic the human disease and survive beyond the neonatal period, are needed. We identified a spontaneous, autosomal recessive mutation (Lamc2 jeb) due to a Murine Leukemia Virus long terminal repeat insertion in Lamc2 that results in a hypomorphic allele with reduced levels of LAMC2 protein. These mutant mice develop a progressive blistering disease validated at the gross and microscopic levels to closely resemble generalized non-Herlitz JEB. The Lamc2 jeb mice display additional extracutaneous features such as loss of bone mineralization and abnormal teeth, as well as a respiratory phenotype that is recognized but not as well characterized in humans. This model faithfully recapitulates human JEB and provides an important preclinical tool to test novel therapeutic approaches.

show abstract

Section: Introductionmentioning

confidence: 92%

A Mouse Model of Generalized Non-Herlitz Junctional Epidermolysis Bullosa

Bubier

Sproule

Alley

et al. 2010

Journal of Investigative Dermatology

View full text Add to dashboard Cite

show abstract

“…Ultrastructurally, the site of blistering is the sublamina densa zone (Figure d). In humans, cats, dogs, sheep, cattle and goats with recessive DEB, the anchoring fibrils are scarce and rudimentary. Dystrophic epidermolysis bullosa with similar ultrastructural alterations has also been reported in ostriches, although the mode of inheritance was not determined .…”

Section: Dystrophic Epidermolysis Bullosamentioning

confidence: 99%

Epidermolysis bullosa in animals: a review

Medeiros

Riet-Correa

2014

Veterinary Dermatology

View full text Add to dashboard Cite

Epidermolysis bullosa (EB) is a hereditary mechanobullous disease of animals and humans, characterized by an extreme fragility of the skin and mucous membranes. The main feature of EB in humans and animals is the formation of blisters and erosions in response to minor mechanical trauma. Epidermolysis bullosa is caused by mutations in the genes that code for structural proteins of the cytoskeleton of the basal keratinocytes or of the basement membrane zone. Based on the ultrastructural levels of tissue separation, EB is divided into the following three broad categories: epidermolysis bullosa simplex, junctional epidermolysis bullosa and dystrophic epidermolysis bullosa. Human types of EB are divided into several subtypes based on their ultrastructural changes and the mode of inheritance; subtypes are not fully established in animals. In humans, it is estimated that EB affects one in 17,000 live births; the frequency of EB in different animals species is not known. In all animal species, except in buffalo with epidermolysis bullosa simplex, multifocal ulcers are observed on the gums, hard and soft palates, mucosa of the lips, cheek mucosa and dorsum of the tongue. Dystrophic or absent nails, a frequent sign seen in human patients with EB, corresponds to the deformities and sloughing of the hooves in ungulates and to dystrophy or atrophy of the claws in dogs and cats. This review covers aspects of the molecular biology, diagnosis, classification, clinical signs and pathology of EB reported in animals.

show abstract

“…As yet, no model exists for DDEB. Although an Akita dog was suggested to have DDEB [19], the mode of inheritance could not be conclusively determined.…”

Section: Introductionmentioning

confidence: 99%

Rat Model for Dominant Dystrophic Epidermolysis Bullosa: Glycine Substitution Reduces Collagen VII Stability and Shows Gene-Dosage Effect

et al. 2013

View full text Add to dashboard Cite

Dystrophic epidermolysis bullosa, a severely disabling hereditary skin fragility disorder, is caused by mutations in the gene coding for collagen VII, a specialized adhesion component of the dermal-epidermal junction zone. Both recessive and dominant forms are known; the latter account for about 40% of cases. Patients with dominant dystrophic epidermolysis bullosa exhibit a spectrum of symptoms ranging from mild localized to generalized skin manifestations. Individuals with the same mutation can display substantial phenotypic variance, emphasizing the role of modifying genes in this disorder. The etiology of dystrophic epidermolysis bullosa has been known for around two decades; however, important pathogenetic questions such as involvement of modifier genes remain unanswered and a causative therapy has yet to be developed. Much of the failure to make progress in these areas is due to the lack of suitable animal models that capture all aspects of this complex monogenetic disorder. Here, we report the first rat model of dominant dystrophic epidermolysis bullosa. Affected rats carry a spontaneous glycine to aspartic acid substitution, p.G1867D, within the main structural domain of collagen VII. This confers dominant-negative interference of protein folding and decreases the stability of mutant collagen VII molecules and their polymers, the anchoring fibrils. The phenotype comprises fragile and blister-prone skin, scarring and nail dystrophy. The model recapitulates all signs of the human disease with complete penetrance. Homozygous carriers of the mutation are more severely affected than heterozygous ones, demonstrating for the first time a gene-dosage effect of mutated alleles in dystrophic epidermolysis bullosa. This novel viable and workable animal model for dominant dystrophic epidermolysis bullosa will be valuable for addressing molecular disease mechanisms, effects of modifying genes, and development of novel molecular therapies for patients with dominantly transmitted skin disease.

show abstract

Dystrophic form of inherited epidermolysis bullosa in a dog (Akita Inu)

Cited by 23 publications

References 17 publications

A Mouse Model of Generalized Non-Herlitz Junctional Epidermolysis Bullosa

A Mouse Model of Generalized Non-Herlitz Junctional Epidermolysis Bullosa

Epidermolysis bullosa in animals: a review

Rat Model for Dominant Dystrophic Epidermolysis Bullosa: Glycine Substitution Reduces Collagen VII Stability and Shows Gene-Dosage Effect

Contact Info

Product

Resources

About