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.

DOI

10.13028/M2KW24

Rights and Permissions

Copyright is held by the author, with all rights reserved.

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