Dissecting the role of sarcomere assembly in the pathology of human congenital myopathy

This thesis investigates the molecular mechanisms underlying sarcomere assembly, and has the potential for future development of treatments for genetic muscle diseases. By utilising forward and reverse genetic approaches, this thesis characterizes novel zebrafish mutants. From an ENU screen, a zebrafish mutant in Abce1 was identified, demonstrating the importance of translational regulation for the formation of muscle. Using CRISPR/Cas9 technology, zebrafish mutants were generated targeting CapZ subunits. Capza1b is essential for stabilising terminal actin microfilaments, attaching sarcomeres to the myotendionous junction and allowing force to be transferred. Additionally this thesis identifies CAPZA2 as a novel potential candidate gene for genetically unresolved nemaline myopathy.