Everyday movement, whether sitting or running a marathon, exerts stressful forces on myotendinous junctions (MTJs). As the sites which skeletal muscle fibers anchor to surrounding extracellular matrix (ECM) material of tendon, MTJs need to maintain homeostasis under stress for muscle to function normally. Human congenital muscular dystrophies (CMDs) are a heterogeneous group of diseases that disrupt muscle homeostasis, are severely debilitating, and currently have no cure. In many CMDs, genetic mutations effect cell adhesion complexes located at the MTJ. The adherence of muscle fibers’ cytoskeleton to the extracellular matrix (ECM) is weakened when these complexes as compromised. Many genes resulting in muscular dystrophies are currently identified, yet the fundamental cell processes underlying muscle formation and attachment are chiefly unknown. This gap ! in knowledge results in a lack of tissue specific treatments. This project aims to research whether the overexpression of nicotinamide ribose kinase 2b (Nrk2b) enzyme, required in a salvage pathway to generate NAD+ and aid in the regulation of muscle cell adhesion, can be exploited to rescue a form of congenital muscular dystrophy in the zebrafish model organism. Exploring this pathway will potentially lead to knowledge that can be applied to gene therapies, using the Nrk2b kinase as a pharmacological target, and deepening knowledge of the zebrafish model system for the study of muscle disease.
Burgess, Anna, "Characterization of Nrk2b Overexpression in a Transgenic Zebrafish Congenital Muscular Dystrophy Model" (2012). Honors College. 95.