EPIDERMOLYSIS BULLOSA IN THE DOG

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. One male and two female puppies from a litter of seven Labrador Retrievers were presented with clinical signs and histopathologic findings consistent with functional epidermolysis bullosa. Severe erosions and ulcers of the oral mucosa, the footpads, and the inside of the pinnae were seen on physical examination. Microscopic evaluation of skin and footpad biopsies was suggestive ofjunctional epidermolysis bullosa (JEB). Pedigree analysis was suggestive of an autosomal recessive inheritance. All of the affected dogs have been humanely euthanized or have died in the meantime but we are attempting to expand the colony by breeding the carrier sire to one of our normal females. Junctional epidermolysis bullosa is characterized by fragility at the dermal-epidermal junction and can be due to a number of protein defects at this level. While many of the molecular defects have been elucidated in humans, to our knowledge only two descriptions of canine JEB exist in the veterinary literature. The initial approach for this project was first to characterize the JEB in the Labrador retriever. We have clinically evaluated the affected dogs and obtain skin biopsies for histopathology, electron microscopy, immunohistochemistry, and tissue culture. Immunohistochemical and electronmicroscopic studies have revealed a defect in collagen VII. We are now in the process of sequencing the canine collagen VII gene to develop a genetic test. The ultimate goal is to provide a large animal model with a genetic skin disease for gene therapy trials.