It is now possible to isolate genes and understand disease mechanisms in terms of the underlying molecular derangements. This knowledge is essential to develop and test protein, somatic cell gene, and stem cell therapies for human genetic diseases. The full scope of understanding the pathogenesis of these disorders and testing therapy cannot be realized without authentic (gene-homologous, orthologous) animal models for the studies that are not possible for ethical and practical reasons in human patients. Gene knockout technology in mice has provided a valuable source, but additional models are needed for studies requiring long-lived animals of larger size and diverse genetic background to be able to monitor efficacy and safety long-term. A reservoir of such diseases is present in existing dog and cat breeds that are relatively inbred but that retain genetic heterogeneity similar to that present in the Old Order Amish and Ashkenazi Jewish populations. The objective of this grant is to continue to serve as a National and International Referral Center to identify, characterize, verify, preserve, and make available for research new and existing large animal models of human genetic disease. These models involve defects in homologous gene loci having the same molecular and clinical phenotypes as in human patients. Models offering new opportunities to investigate disease pathogenesis and approaches to therapy will be emphasized in consultation with an Advisory Committee. The Center will provide the clinical, pathological, and molecular genetic studies required to discover important large animal models, including, as a new direction, those with complex inheritance, and establish their homology with the human disorder. Verified models will be made available to other investigators for a nominal fee-for-service in the form of DNA, cells, frozen semen, and breeding stock. We will also serve as a resource for normal dogs and cats and their tissues, and we will continue to offer a facility and expertise for investigators to perform pathogenetic and therapy experiments in dog and cat models on a Program Income Fund, fee-for-service basis.

Public Health Relevance

This Referral Center finds, characterizes, and makes available dog and cat gene-homologous models of human genetic disorders for the study of the pathogenesis of disease and the development of effective, safe therapies for human patients.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
Animal (Mammalian and Nonmammalian) Model, and Animal and Biological Material Resource Grants (P40)
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Special Emphasis Panel (ZTR1-CM-6 (01))
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O'Neill, Raymond R
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University of Pennsylvania
Schools of Veterinary Medicine
United States
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Callan, Mary Beth; Haskins, Mark E; Wang, Ping et al. (2016) Successful Phenotype Improvement following Gene Therapy for Severe Hemophilia A in Privately Owned Dogs. PLoS One 11:e0151800
Mauldin, Elizabeth A; Wang, Ping; Olivry, Thierry et al. (2016) Epidermolysis bullosa simplex in sibling Eurasier dogs is caused by a PLEC non-sense variant. Vet Dermatol :
Yoon, Sea Young; Bagel, Jessica H; O'Donnell, Patricia A et al. (2016) Clinical Improvement of Alpha-mannosidosis Cat Following a Single Cisterna Magna Infusion of AAV1. Mol Ther 24:26-33
Flanagan-Steet, Heather; Aarnio, Megan; Kwan, Brian et al. (2016) Cathepsin-Mediated Alterations in TGFß-Related Signaling Underlie Disrupted Cartilage and Bone Maturation Associated With Impaired Lysosomal Targeting. J Bone Miner Res 31:535-48
Simonaro, Calogera M; Tomatsu, Shunji; Sikora, Tracy et al. (2016) Pentosan Polysulfate: Oral Versus Subcutaneous Injection in Mucopolysaccharidosis Type I Dogs. PLoS One 11:e0153136
Bradbury, Allison M; Bagel, Jessica H; Jiang, Xuntian et al. (2016) Clinical, electrophysiological, and biochemical markers of peripheral and central nervous system disease in canine globoid cell leukodystrophy (Krabbe's disease). J Neurosci Res 94:1007-17
Euler, C C; Lee, J H; Kim, H Y et al. (2016) Survey of Two New (Kai 1 and Kai 2) and Other Blood Groups in Dogs of North America. J Vet Intern Med 30:1642-1647
Hinderer, Christian; Bell, Peter; Louboutin, Jean-Pierre et al. (2016) Neonatal tolerance induction enables accurate evaluation of gene therapy for MPS I in a canine model. Mol Genet Metab 119:124-30
Gurda, Brittney L; De Guilhem De Lataillade, Adrien; Bell, Peter et al. (2016) Evaluation of AAV-mediated Gene Therapy for Central Nervous System Disease in Canine Mucopolysaccharidosis VII. Mol Ther 24:206-16
Euler, Catharina C; Raj, Karthik; Mizukami, Keijiro et al. (2016) Xenotransfusion of anemic cats with blood compatibility issues: pre- and posttransfusion laboratory diagnostic and crossmatching studies. Vet Clin Pathol 45:244-53

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