Mdx mouse

The Mdx mouse is a widely used animal model for studying Duchenne muscular dystrophy (DMD), a severe form of muscular dystrophy caused by mutations in the dystrophin gene. The Mdx mouse carries a point mutation in the dystrophin gene, leading to the absence of functional dystrophin protein, which mimics the genetic defect seen in human DMD patients.

Background

Duchenne muscular dystrophy is an X-linked recessive disorder characterized by progressive muscle degeneration and weakness. It primarily affects boys, with symptoms usually appearing in early childhood. The absence of dystrophin, a protein that helps stabilize and protect muscle fibers, leads to muscle damage and eventual loss of muscle function.

Genetic Characteristics

The Mdx mouse was first identified in the 1980s as a spontaneous mutation in the C57BL/10 mouse strain. The mutation is a single nucleotide change in exon 23 of the dystrophin gene, resulting in a premature stop codon and the production of a truncated, non-functional dystrophin protein. This genetic defect is analogous to the mutations found in human DMD patients, making the Mdx mouse an invaluable model for studying the disease.

Phenotypic Features

Mdx mice exhibit many of the pathological features of DMD, including muscle fiber necrosis, regeneration, and fibrosis. However, unlike human patients, Mdx mice have a relatively mild phenotype and do not exhibit the same degree of muscle weakness or shortened lifespan. This discrepancy is thought to be due to compensatory mechanisms in mice, such as the upregulation of utrophin, a dystrophin-related protein.

Research Applications

The Mdx mouse model is extensively used in preclinical research to:

• Study the pathophysiology of DMD and the role of dystrophin in muscle function.
• Evaluate potential therapeutic strategies, including gene therapy, exon skipping, and pharmacological interventions.
• Investigate the molecular and cellular mechanisms underlying muscle degeneration and regeneration.

Limitations

While the Mdx mouse is a valuable tool for DMD research, it has limitations. The mild phenotype and the presence of compensatory mechanisms in mice can complicate the translation of findings to human patients. Researchers often use additional models, such as the Golden Retriever muscular dystrophy (GRMD) dog, to complement studies in Mdx mice.

Also see

• Duchenne muscular dystrophy
• Dystrophin
• Utrophin
• Gene therapy
• Exon skipping