Generating a targeted mutation resource in zebrafish

Peter Currie, PhD

Monash University (Victoria, Australia)

Dr. Currie is a Professor at Monash University in the Australian Regenerative Medicine Institute.

Past Projects

Objective: 
Creation and characterization of a dysferlin deficient zebrafish model

Mutations in the Dysferlin gene, which encodes a member of the "Ferlin-1 like" class of lipid binding proteins, result in three clinically distinct human muscular dystrophies: LGMD2B; Miyoshi myopathy; and a distinct distal anterior compartment myopathy. Mice with dysferlin deficiency have become accepted models for LGMD2B/Miyoshi myopathy and have been utilized to understand the progression of this disease. However the disease phenotype progresses slowly in mice, similar to human patients, which prohibits rapid screening of potential therapeutics to counter loss of dysferlin. Therefore, new tools and animal models must be developed that are more amenable to rapid therapeutic screening. Zebrafishare one model that have been developed to fill such a gap. However, there are no known mutations in zebrafish Dysferlin. Recently, we and others, have identified a zebrafish orthologue of Dysferlin present within the zebrafish genome that possesses identity with mammalian Dysferlin. Thus, it appears likely that a similar Dysferlin-dependent repair process operates in zebrafish, and that this activity is represented by a single orthologous gene.

Thus, this gene presents as a good candidate for generating a specific human disease model by a specific reverse genetic approaches. The aim of this project is the generation and preliminary analysis of a LGMD2B/Miyoshi zebrafish model using zinc-finger technology.