The central purpose of the Animal Models Core is to provide the affiliated investigators with the appropriate genotype and strain of rodent for the proposed studies, and to provide a range of immunological assays on animals inject with adenoviral vectors. The Animal Models Core is specifically dedicated to investigations of novel strategies of gene delivery to aged or dystrophic striated muscle, as well as mechanistic based evaluations of the effects of genetic modification of dystrophin on muscle cell mechanical properties in young and aged animals. All rodents will be raised and maintained under specific-pathogen-free conditions at the University of Michigan AAALAC-accredited animal facility. In addition to maintaining stocks of animals for testing, the core will conduct a detailed life span analysis of the dystrophic mdx mouse. This core lab will also handle all the immunology required for analysis of adenoviral vector development. A goal of our new vector design is to develop an adenoviral based vector that does not trigger a strong immune response in host animals, particularly a cytotoxic T-cell mediated response. Animals that are injected with virus will be used not only to assess the longevity and functional consequences of gene expression, but will also be tested for potential immune responses against the virus and the transgene being delivered. This analysis will involve CTL-assays against adenoviral and transgene proteins, as well as B cell mediated humoral immune responses against the same proteins.
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