Mdx mouse

Despite its widespread use, the mdx mouse has several important limitations as a model for Duchenne muscular dystrophy. The mdx mouse displays a considerably milder phenotype than human DMD patients, largely due to the compensatory upregulation of utrophin^[6].

In 2016, despite decades of successful preclinical studies in mdx mice, many promising therapies failed in human clinical trials, highlighting the translational gap between the mouse model and human disease^[7].

To overcome these limitations, researchers have developed improved models such as the mdx/utrophin double knockout mouse, which more closely resembles the severe human DMD phenotype, and humanized mdx models that allow testing of human-specific therapies such as exon skipping drugs^[6].

The mdx mouse has been at the forefront of CRISPR-Cas9 gene editing research for Duchenne muscular dystrophy. In 2014, the first successful correction of the dystrophin mutation using CRISPR-Cas9 was demonstrated directly in mdx mice, marking a historic milestone in gene editing therapy^[9].

In 2018, researchers used AAV-delivered CRISPR-Cas9 to restore dystrophin expression in mdx mice following a single systemic injection, demonstrating the remarkable potential of this approach^[10].

These results in mdx mice directly led to the first CRISPR-based clinical trials for DMD in human patients, representing a direct translation from mouse model to human medicine^[5].