GSBS Dissertations and Theses
ORCID ID
0000-0001-5653-750X
Publication Date
2016-09-26
Document Type
Master's Thesis
Academic Program
Translational Science
Department
Neurology
First Thesis Advisor
Robert H. Brown, Jr., DPhil, MD
Keywords
dysferlin, muscular dystrophy, membrane resealing
Abstract
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.
Repository Citation
Fridman, L. Histopathological Characterization of the Dystrophic Phenotype and Development of Therapeutic Candidates for a Gene Therapy Pre-Clinical Study in Dysferlin Deficient Mice. (2016). University of Massachusetts Medical School. GSBS Dissertations and Theses. Paper 881. DOI: 10.13028/M2KW24. https://escholarship.umassmed.edu/gsbs_diss/881
DOI
10.13028/M2KW24
DOI Link
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