Histopathological Characterization of the Dystrophic Phenotype and Development of Therapeutic Candidates for a Gene Therapy Pre-Clinical Study in Dysferlin Deficient Mice
Authors
Fridman, LeticiaFaculty Advisor
Robert H. Brown, Jr., DPhil, MDAcademic Program
Translational ScienceUMass Chan Affiliations
NeurologyDocument Type
Master's ThesisPublication Date
2016-09-26
Metadata
Show full item recordAbstract
Dysferlin deficient muscular dystrophy is a devastating disease that leads to loss of mobility and quality of life in patients. Dysferlin is a 230 kD protein primarily expressed in skeletal muscle that functions in membrane resealing. Dysferlin loss of function leads to a decrease in the membrane resealing response after injury in skeletal muscle, which is thought to cause degeneration of the musculature over time. Dysferlin cDNA is 7.4 kb and exceeds AAV packaging capacity of ~ 5kb. This thesis focuses on the generation of mini dysferlin mutants that can be packaged in AAV for downstream testing of therapeutic efficacy. In addition, this thesis creates the groundwork for preclinical studies in mice that can potentially be translated to human patients. A mouse model for dysferlin deficiency was characterized and key disease phenotypes were identified. In addition, cell lines carrying a genetically encoded calcium indicator protein, gCaMP, were established to measure mini dysferlin resealing capacity and for downstream testing in vivo.DOI
10.13028/M2KW24Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32258Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/M2KW24