EPIDERMOLYSIS BULLOSA IN THE DOG

狗的大疱性表皮松解症

• 批准号: 7391963
• 负责人: MARGRET L CASAL
• 金额: $ 0.13万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7391963
• 关键词: EPIDERMOLYSIS; BULLOSA; DOG

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。从七个拉布拉多猎犬的垃圾中的一只雄性和两只幼犬出现了临床体征和组织病理学的发现与功能性表皮溶液一致。在体格检查中，可以看到口腔粘膜，脚板和小针刺内部的严重侵蚀和溃疡。皮肤和脚踏活检的显微镜评估暗示性表皮溶液Bullosa（JEB）。血统分析暗示了常染色体隐性遗传。同时，所有受影响的狗都被人性化的安乐死或死亡，但我们试图通过将载体父亲繁殖到我们的一位正常女性来扩大殖民地。连接性表皮溶液Bullosa的特征是皮肤表皮连接处的脆弱性，可能是由于该水平的许多蛋白质缺陷引起的。尽管许多分子缺陷已经在人类中阐明了，但据我们所知，兽医文献中只有两个描述犬Jeb。该项目的最初方法是首先要在拉布拉多猎犬中表征JEB。我们已经在临床上评估了受影响的狗，并获得了组织病理学，电子显微镜，免疫组织化学和组织培养的皮肤活检。免疫组织化学和电子显微镜研究表明胶原蛋白VII缺陷。现在，我们正在对犬胶原蛋白VII基因进行测序以开发基因检测。最终目标是为基因治疗试验的遗传皮肤疾病提供大型动物模型。