LETHAL ACRODERMATITIS

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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.