The Need

There has yet to be a DMD animal model that bridges the gap between cost effectiveness and scientific relevance. This new rabbit model does that.

The Technology

DMD is a lethal genetic disease characterized by progressive muscle weakness and muscle wasting. There are several animal models for DMD, including mice, dog and pig. The most widely used mouse model of DMD is mdx mice, which show typical features of muscular dystrophy, however, they do not fully recapitulate human DMD pathology. For example, human DMD patients develop cardiomyopathy and many die from cardiac failure, but the mdx mice for the most part, live a normal lifespan and do not present cardiac dysfunction until a year later. The large animal models such as dog and pig are better in phenotype presentation but the high cost associated with using them (such as longer gestational periods and higher colony maintenance costs) make it hard on researchers.

Therefore, an attempt to generate a new animal model of DMD using rabbits was made. The DMD-KO rabbits were generated by microinjection of CBE mRNA and sgRNA targeting exon 51 of the DMD gene into rabbit zygotes. The founder rabbits were genotyped by direct DNA sequencing. They showed reduced body weight, increased premature death, reduced physical activity, increased serum creatine kinase levels, and decreased ejection fraction. Many of these pathological features are also seen in human counterparts, making it a useful model to study the disease mechanisms, biomarkers and preclinical therapeutic testing. This model addresses the concerns of the larger animal model by being cost effective and having a low gestation period, and it addresses the smaller animal model concerns by having a more similar pathology to humans.

Commercial Applications

• Pre-clinical drug testing
• Genetic disease modeling
• Could be useful in other clinical applications

Benefits/Advantages

• More cost effective compared to larger animal models
• Most scientifically accurate compared to smaller animal models
• Easily maintained colonies for testing