Animal Models Core. Animal models of human disease are a critical component in the development of effective gene therapies. Genetically defined animal models that reproduce the clinical manifestations of a disease help to elucidate the pathophysiologically relevant cellular targets for gene therapy and aid in the development and testing of gene vector technologies for therapeutic efficacy. The Animal Models Core has provided support to investigators who use animal models to develop gene therapies for several genetic diseases, with an emphasis on Cystic Fibrosis (CF). In this regard, the Animal Models Core provides centralized production, care, breeding, genotyping, and quality control of transgenic lines for use by investigators in the Center. The Core has also provided a mechanism for the receipt and distribution of new experimental transgenic and knockout models to and from collaborators at other institutions. BL2 animal containment facilities for experiments with recombinant viruses are consolidated within the Core for use by investigators of the Center. Centralized technicians within the Core facilitate more technically challenging aspects of gene therapy research in animals, such as vector administration and tissue harvesting. For CF based research, the Core places several animal models at the disposal of Center investigators, including colonies of pathogen-free CF mice as well as tracheobronchial xenograft models that are generated from primary human CF and non-CF airway cells or from native pig and ferret airway implants. Recently, the Core has been instrumental in the development of CFTR-deficient ferret and pig models. In this context, the Core has played a major role in developing technologies for cloning ferrets by nuclear transfer and has also aided in the cumbersome screening of primary pig and ferret fibroblasts for rAAV-mediated CFTR gene-targeting events. The generation of these two larger CF animal models has had a significant impact on the future directions of the Animal Models Core. For example, Center investigators studying innate immunity in the airway have benefited greatly from xenograft model systems; however, the CF pig and ferret models now provide a myriad of additional opportunities in this regard. Such studies on the basic pathobiology of CF airway disease will lead to the identification of the relevant cellular targets and CFTR functions in the lung that are necessary for successful gene therapy approaches. Although this Core directs the majority of its efforts toward gene therapy of CF, it will also play a broader role in the development of gene therapies for several other genetic diseases of programmatic emphasis at this Center. The main responsibilities of the Core will be: * Generation of transgenic mice * Genotyping of transgenic and knockout animals * Rederival and cryopreservation of genetic stocks * Assistance in gene delivery and tissue harvesting in animal experiments * Generation of human bronchial xenograft models and tracheal xenograft models from other species * Maintenance distribution of genetic animal models (limited to mice and the new CF ferret models)

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK054759-14
Application #
8564799
Study Section
Special Emphasis Panel (ZDK1-GRB-1 (J2))
Project Start
1998-09-30
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
14
Fiscal Year
2012
Total Cost
$218,390
Indirect Cost
$74,552
Name
University of Iowa
Department
Type
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
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