LETHAL ACRODERMATITIS

致命性肢端皮炎

• 批准号: 7391966
• 负责人: MARGRET L CASAL
• 金额: $ 0.07万
• 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/7391966
• 关键词: LETHAL; ACRODERMATITIS

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. Two bull terriers were presented with classic signs of lethal acrodermatitis, which is a syndrome characterized clinically by retarded growth, progressive acrodermatitis, chronic pyoderma and paronychia, diarrhea, pneumonia, abnormal behavior, and death by 15 months of age. Because of clinical and pathological similarities, it is thought that lethal acrodermatitis in the dog is homologous to acrodermatitis enteropathica in humans and cattle. Thus, we are in the process of sequencing ZIP4, the putative causative gene. We have determined zinc concentrations in all tissues of the body and comparing them to normal levels obtained from a normal age-matched bull terrier. We have established a collaboration with Dr. Arthur Grider from the Department of Foods and Nutrition at the University of Georgia. He has been using the fibroblasts obtained from our affected dogs to study the LAD proteome and determine how this mutation affects protein expression. Their interest is in identifying the biochemical defect as well as determining whether the mutation affects the physiological pathways for cellular zinc homeostasis. They have performed 2DPAGE on the fibroblasts, and plan to run all other tissues we have sent.

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。两只牛头梗表现出典型的致死性肢端皮炎症状，临床表现为生长迟缓、进行性肢端皮炎、慢性脓皮病和甲沟炎、腹泻、肺炎、行为异常和15月龄死亡。由于临床和病理上的相似性，人们认为狗的致死性肢端皮炎与人类和牛的肠病性肢端皮炎是同源的。因此，我们正在对假定的致病基因ZIP4进行测序。我们已经确定了身体所有组织中的锌浓度，并将其与正常年龄匹配的牛头梗的正常水平进行比较。我们与乔治亚大学食品与营养系的Arthur Grider博士建立了合作关系。他一直在使用从我们受影响的狗身上获得的成纤维细胞来研究LAD蛋白质组，并确定这种突变如何影响蛋白质表达。他们的兴趣在于确定生化缺陷以及确定突变是否影响细胞锌稳态的生理途径。他们已经对成纤维细胞进行了2DPAGE，并计划对我们送来的所有其他组织进行检测。