EPIDERMOLYSIS BULLOSA IN THE DOG

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。一窝七只拉布拉多寻回犬中的一只雄性和两只雌性小狗被呈现出与功能性大疱性表皮松解症一致的临床症状和组织病理学结果。体格检查发现口腔粘膜、足垫和耳廓内侧有严重的侵蚀和溃疡。皮肤和足垫活检的显微镜评估提示大疱性交界性表皮松解症(JEB)。家系分析提示为常染色体隐性遗传。所有受影响的狗都已被人道安乐死或在此期间死亡，但我们正试图通过将携带者繁殖到一只正常的雌性狗来扩大种群。交界性大疱性表皮松解症的特征是真皮-表皮交界处的脆性，可能是由于这一水平上的许多蛋白质缺陷所致。虽然许多分子缺陷在人类中已经被阐明，但据我们所知，在兽医文献中只有两种关于犬类Jeb的描述。这个项目的最初方法是首先描述拉布拉多寻回犬的杰布。我们已经对受影响的狗进行了临床评估，并获得了皮肤活检的组织病理学、电子显微镜、免疫组织化学和组织培养。免疫组织化学和电子显微镜研究已经发现了VII型胶原的缺陷。我们现在正在对狗的VII型胶原基因进行测序，以开发一种遗传测试。最终目标是为基因治疗试验提供一种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.