EHLERS-DANLOS 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。一只雌性拉布拉多猎犬的临床症状和组织病理学结果与埃勒斯-丹洛斯综合征(EDS)相一致。皮肤高度伸展，容易撕裂，创伤很小。两个髋关节都在生命早期就脱臼了。皮肤镜检提示EDS。家系分析提示一种新的常染色体显性遗传。我们最近将受影响的雌性交配给了我们的一只正常雄性，试图扩大蜂群。EDS的特点是胶原脆弱，可能是由于这一水平上的许多蛋白质缺陷造成的。虽然一些分子缺陷在人类中已经被阐明，但据我们所知，在患有EDS的狗身上还没有确定这些缺陷。这个项目的最初方法是描述拉布拉多寻回犬的EDS特征。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。正在进行的免疫组织化学研究应该在今年夏天结束前完成，有了这些结果，我们应该能够开始对致病基因进行测序。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. A female Labrador retriever presented with clinical signs and histopathologic findings consistent with the Ehlers-Danlos syndrome (EDS). The skin was hyperextensible and tore easily with minimal trauma. Both hip joints were luxated early in life. Microscopic evaluation of skin was suggestive of EDS. Pedigree analysis was suggestive of a new autosomal dominant inheritance. We have recently bred the affected female to one of our normal males in an attempt to expand the colony. EDS is characterized by collagen fragility and can be due to a number of protein defects at this level. While some of the molecular defects have been elucidated in humans, to our knowledge none of them have been determined in dogs with EDS. The initial approach for this project is to characterize the EDS in the Labrador retriever. We have clinically evaluated the affected dogs and obtain skin biopsies for histopathology, electron microscopy, immunohistochemistry, and tissue culture. Ongoing immunohistochemical studies should be completed by the end of the summer of this year and with these results we should be able to begin sequencing the causative gene. The ultimate goal is to provide a large animal model with a genetic skin disease for gene therapy trials.