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.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Animal (Mammalian and Nonmammalian) Model, and Animal and Biological Material Resource Grants (P40)
Project #
8P40OD010939-28
Application #
8231273
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
O'Neill, Raymond R
Project Start
1985-09-20
Project End
2013-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
28
Fiscal Year
2012
Total Cost
$713,478
Indirect Cost
$253,973
Name
University of Pennsylvania
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Shao, Hongguang; Li, Xinshe; Lok, James B (2017) Heritable genetic transformation of Strongyloides stercoralis by microinjection of plasmid DNA constructs into the male germline. Int J Parasitol 47:511-515
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