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
Fyfe, John C; Hemker, Shelby L; Frampton, Alycia et al. (2018) Inherited selective cobalamin malabsorption in Komondor dogs associated with a CUBN splice site variant. BMC Vet Res 14:418
Wang, Ping; Mazrier, Hamutal; Caverly Rae, Jessica et al. (2018) A GNPTAB nonsense variant is associated with feline mucolipidosis II (I-cell disease). BMC Vet Res 14:416
Genger, Seiche C; Mizukami, Keijiro; Martin, Michael P et al. (2018) Mucopolysaccharidosis IIIB (Sanfilippo syndrome B) in a commercial emu (Dromaius novaehollandiae) flock. Avian Pathol 47:100-107
Hinderer, Christian; Bell, Peter; Katz, Nathan et al. (2018) Evaluation of Intrathecal Routes of Administration for Adeno-Associated Viral Vectors in Large Animals. Hum Gene Ther 29:15-24
Wang, P; Henthorn, P S; Galban, E et al. (2018) Canine GM2-Gangliosidosis Sandhoff Disease Associated with a 3-Base Pair Deletion in the HEXB Gene. J Vet Intern Med 32:340-347
Szelecsenyi, Arlette Cornelia; Giger, Urs; Golini, Lorenzo et al. (2017) Survival in 76 cats with epilepsy of unknown cause: a retrospective study. Vet Rec 181:479
Inal-Gültekin, Güldal; Topta?-Hekimo?lu, Bahar; Görmez, Zeliha et al. (2017) Myophosphorylase (PYGM) mutations determined by next generation sequencing in a cohort from Turkey with McArdle disease. Neuromuscul Disord 27:997-1008
Bauer Jr, Thomas R; Pratt, Suzanne M; Palena, Christina M et al. (2017) Feline leukocyte adhesion (CD18) deficiency caused by a deletion in the integrin ?2 (ITGB2) gene. Vet Clin Pathol 46:391-400
Casal, Margret L; Wang, Ping; Mauldin, Elizabeth A et al. (2017) A Defect in NIPAL4 Is Associated with Autosomal Recessive Congenital Ichthyosis in American Bulldogs. PLoS One 12:e0170708
Hilton, Stephanie; Mizukami, Keijiro; Giger, Urs (2017) [Cystinuria caused by a SLC7A9 missense mutation in Siamese-crossbred littermates in Germany]. Tierarztl Prax Ausg K Kleintiere Heimtiere 45:265-272

Showing the most recent 10 out of 101 publications