About the RCAM
For many lethal or debilitating genetic disorders in patients there are no satisfactory therapies. The critical barriers to developing effective treatments for genetic diseases in humans and animals include limited natural history studies, an insufficient understanding of how genotype and phenotype correlate with disease, a paucity of validated surrogate markers, and the dearth of potential therapies that substantially improve disease in animal models. These barriers are partially overcome by studying naturally occurring large animal models (canine and feline) of human genetic disease for which breeding colonies are developed and natural history, clinicopathological, and histological data are collected. Animal models allow for the studies necessary to unravel the pathogenic mechanisms involved in disease progression.
In 1974, the Referral Center for Animal Models of Human Genetic Disease (RCAM) was established at the University of Pennsylvania with the overall objective to serve as a national referral and resource center to discover, characterize, maintain breeding colonies, and make available dog and cat models with hereditary diseases homologous to those found in human patients that can be used to translate preclinical trials from kennel to clinic. The naturally occurring animal models currently available represent true orthologs of their respective human disease, involving defects in homologous genes resulting in similar molecular, biochemical, pathological, and clinical phenotype as in human patients.
In addition to the naturally-occurring animal models identified and made available through RCAM, we can create large animal models of human disease by using CRISPR/Cas9 methods in collaboration with the Center for Animal Transgenesis and Germ Cell Research Core Facility.
Indeed, large animal models serve as an important intermediate for the assessment of therapeutic strategies by allowing for repeated sampling of fluids and tissue, evaluation of disease progression and safety of therapy using the same equipment and techniques used in pediatric and general human patient populations, accurate biodistribution studies due to increased brain and body size, and long-term efficacy and safety studies due to their prolonged lifespan.
Although non-human primates, sheep, and pig models also share some of these attributes, naturally occurring diseases are rarely identified in non-human primates, and the vast behavioral, clinicopathological, physiological, and anatomical knowledge available regarding dogs and cats far surpasses what is available in ovine and porcine species. Finally, the tremendous expertise of veterinarians and the state of the art veterinary facilities available provide an unparalleled capability to characterize naturally occurring diseases in dogs and cats.