Canine Model of Duchenne Muscular Dystrophy.

Abstract

Dystrophin-deficient canines are the best-characterized large animal model for Duchenne muscular dystrophy (DMD). Unlike dystrophin-null mice, affected dogs display many phenotypical features of human patients. Furthermore, dogs' body size and body weight are much closer to humans than those of mice's. These features make affected canines an excellent model system for studying pathogenic mechanisms of the disease and for testing novel experimental therapeutics. The golden retriever muscular dystrophy (GRMD) dog is the first canine DMD model with a confirmed null mutation in the DMD gene. Since then, dystrophin-deficient dogs have been identified in many different breeds. Research colonies have been established worldwide. Here, we describe our experience in generating and maintaining affected dogs. Adeno-associated virus (AAV) vectors have been used to restore dystrophin expression by gene replacement or gene repair therapies. We provide protocols for intramuscular AAV injection in adult canines and systemic delivery of AAV to neonatal and young adult canines. We also include a muscle biopsy protocol for periodic monitoring of gene transfer before the terminal study.