EPIDERMOLYSIS BULLOSA IN THE DOG

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。从一窝7只拉布拉多猎犬中选出1只雄性和2只雌性幼犬，其临床症状和组织病理学结果与功能性大疱性表皮松解症一致。体格检查发现口腔黏膜、脚垫和耳廓内部有严重的糜烂和溃疡。皮肤和足部活检的显微评价提示结缔性大疱性表皮松解症（JEB）。家谱分析提示常染色体隐性遗传。与此同时，所有受影响的狗都已被人道地安乐死或死亡，但我们正试图通过将携带者父系与我们的一只正常雌性交配来扩大种群。大疱性结缔性表皮松解症的特点是真皮-表皮连接处脆弱，可能是由于该水平上的许多蛋白质缺陷。虽然许多分子缺陷已经在人类中被阐明，但据我们所知，在兽医文献中只有两种犬JEB的描述。该项目的最初方法是首先表征拉布拉多寻回犬的JEB。我们对受影响的狗进行了临床评估，并进行了组织病理学、电子显微镜、免疫组织化学和组织培养的皮肤活检。免疫组织化学和电镜研究显示胶原VII有缺陷。我们目前正在对犬类胶原蛋白VII基因进行测序，以开发一种基因测试。最终目标是为基因治疗试验提供具有遗传性皮肤病的大型动物模型。

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.