It is now possible to isolate genes involved in genetic diseases and understand disease mechanisms in terms of the underlying molecular derangements, and there are encouraging new prospects for therapy for genetic diseases, including somatic cell gene and stem cell therapies. The full scope of understanding and treating genetic diseases in human patients cannot be realized without authentic (gene-homologous, orthologous) animal models for studies 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 to be able to monitor clinical signs, and those with phenotypes more closely resembling the human diseases. A large reservoir of such diseases is present in existing inbred animal populations and can be studied with the cooperation of breeders, veterinarians, and others interested in genetic disease control. We have shown that this resource can be further utilized by providing an accessible Center to ascertain, verify, preserve, and distribute these models of human genetic disease. The objective of this project is to continue to serve as a National Referral Center to identify, characterize, and make available for research new and existing large animal models of human genetic disease. The models sought are primarily among dogs, cats, and non-human primates and 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 novel animal models, including those with complex inheritance, and establish their homology with the human disorder. Verified models will be made available to other investigators at a nominal fee-for-service in the form of DNA, cells, frozen semen, and breeding stock. We will also continue to serve as a resource for normal dogs and cats and their tissues for other investigators, and we will offer a program where outside investigators can perform experiments in dogs and cats in our Resource Center facility, both on a fee-for-service basis.

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)
Project #
Application #
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
O'Neill, Raymond R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
Schools of Veterinary Medicine
United States
Zip Code
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

Showing the most recent 10 out of 83 publications