Development of Dysferlin-Deficient Zebrafish as a Drug Screening Tool

Louis Kunkel, PhD

Children's Hospital Boston (Boston, MA)

Dr. Louis Kunkel is a professor of Genetics and Pediatrics in the Department of Genetics at the Children’s Hospital Boston (Boston, MA).

Past Projects

Objective: 
Use a TALEN nuclease to create a dysferlin null zebrafish for subsequent characterization and screening for small molecule corrective agents

The Zebrafish (Danio rerio) is an excellent animal model for the study genetic disorders due to its biological similarity to humans, advanced molecular genetics, small size, permeability to small molecules and rapid development. Zebrafish with dystrophin mutations have been successfully used in small molecule screens of drugs, which have already been approved for use in humans, to search for compound that might correct the skeletal muscle phenotype of the fish. A new gene targeting approach that employs synthetic TALEN technology represents a powerful means to directly modify genetic loci; such an approach leads to the creation of fish strains that are of great utility in many diverse applications, including in small molecule screens for corrective compounds that can be used to treat the genetic mutants. Direct knockout of specific genes enhances the use of zebrafish as an experimental model for studies of human disease. The TALEN technology is highly reliable and we are collaborating with the Langenau laboratory to use this technology to generate zebrafish that lack dysferlin.