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)

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Center Core Grants (P30)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Iowa
Iowa City
United States
Zip Code
Weldon, Sinéad; McNally, Paul; McAuley, Danny F et al. (2014) miR-31 dysregulation in cystic fibrosis airways contributes to increased pulmonary cathepsin S production. Am J Respir Crit Care Med 190:165-74
Sui, Hongshu; Yi, Yaling; Yao, Jianrong et al. (2014) Quantifying insulin sensitivity and entero-insular responsiveness to hyper- and hypoglycemia in ferrets. PLoS One 9:e90519
Xie, Weiliang; Lynch, Thomas J; Liu, Xiaoming et al. (2014) Sox2 modulates Lef-1 expression during airway submucosal gland development. Am J Physiol Lung Cell Mol Physiol 306:L645-60
Hoegger, Mark J; Awadalla, Maged; Namati, Eman et al. (2014) Assessing mucociliary transport of single particles in vivo shows variable speed and preference for the ventral trachea in newborn pigs. Proc Natl Acad Sci U S A 111:2355-60
Sun, Xingshen; Olivier, Alicia K; Yi, Yaling et al. (2014) Gastrointestinal pathology in juvenile and adult CFTR-knockout ferrets. Am J Pathol 184:1309-22
Keiser, Megan S; Boudreau, Ryan L; Davidson, Beverly L (2014) Broad therapeutic benefit after RNAi expression vector delivery to deep cerebellar nuclei: implications for spinocerebellar ataxia type 1 therapy. Mol Ther 22:588-95
Gu, Xiaoling; Karp, Philip H; Brody, Steven L et al. (2014) Chemosensory functions for pulmonary neuroendocrine cells. Am J Respir Cell Mol Biol 50:637-46
Peng, Xinxia; Alföldi, Jessica; Gori, Kevin et al. (2014) The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease. Nat Biotechnol 32:1250-5
Swiderski, Ruth E; Nakano, Yoko; Mullins, Robert F et al. (2014) A mutation in the mouse ttc26 gene leads to impaired hedgehog signaling. PLoS Genet 10:e1004689
Schultz, Mark L; Tecedor, Luis; Stein, Colleen S et al. (2014) CLN3 deficient cells display defects in the ARF1-Cdc42 pathway and actin-dependent events. PLoS One 9:e96647

Showing the most recent 10 out of 301 publications