MDX Mouse Model Validation Data

This month we’re highlighting one of the most commonly used mouse models to study Duchenne Muscular Dystrophy (DMD) – the MDX mouse model B10.mdx), and explore how our advanced services can support your efficacy studies in DMD.  

The X-linked muscular dystrophy (MDX) mouse mimics the human course of the disease by carrying a spontaneous mutation that results in a truncated dystrophin gene. As a result, MDX mice exhibit hallmark features of DMD: 

• Progressive cycles of muscle degeneration and regeneration, typically observed beginning around three weeks of age.  

• Muscle fibrosis and hypertrophy, reflecting the pathological skeletal muscle remodeling that is typically observed in patients. 

To help evaluate the efficacy of novel treatments for DMD, at InnoSer we leverage our experience in neuromuscular studies, offering specialized research services using the MDX mouse model. By implementing a range of InnoSer’s functional readouts (behavioral testing, clinical biomarkers, histopathology assessments) you can obtain highly translational data on your compound’s in improving skeletal muscle function in DMD mice.  

With a focus on translational outcomes, our functional muscle strength and motor function assays include: 

• Treadmill performance: Assess endurance and fatigue. 

• Rotarod test: Measure coordination and balance. 

• Grip strength testing: Quantify forelimb muscle strength. 

• CatWalk™ Gait Analysis: Examine walking patterns and coordination. 

• Wire Hanging Tests: Evaluate endurance and forelimb strength. 

• Functional Reach Test: Study compensatory motor control mechanisms.

At InnoSer, in line with the literature, we have shown that the MDX mice display skeletal muscle weakness affecting skeletal muscle strength and coordination (Figure 1 and 2). In line, histopathology analyses of the tibialis skeletal muscle show smaller cross-section area (CSA) along with centrally positioned nuclei, confirmative of the degeneration and regeneration cycles of DMD muscles (Figure 3).  

Additionally, InnoSer’s scientists have demonstrated that MDX mice exhibit cognitive impairments under specific conditions, offering opportunities to explore neuromuscular and neurobehavioral interplay (Remmelink et al., 2016; Engelbeen et al., 2021).  

MDX mouse model shows decreased skeletal muscle strength   

FIGURE 1. Wire hanging test. MDX mice (B10.Mdx) perform significantly worse (week 6: P<0.01 and week 7: P<0.05) in the wire hang test compared to healthy controls.   

FIGURE 2. MDX mice (B10.Mdx) show skeletal muscle strength deficits on the functional reach test. Compared to healthy WT controls, MDX mice (aged 7 weeks) score lower on (A) falls and the amount of (B) reaches during the 180-second test period. 

WGA staining can be used to evaluate skeletal muscle morphology changes in the MDX mouse model

FIGURE 3. Histopathology images show differences between the m. tibialis anterior skeletal muscle of wild-type and DMD mouse. Compared to WT (A), DMD (B) mice show centrally located nuclei (DAPI, blue). Centrally located nuclei are hallmarks of skeletal muscle regeneration, and in this model, reflective of the constant remodeling of the skeletal muscle driven by cycles of muscle degeneration and regeneration. In WT mice, nuclei are located at the sarcolemma (WGA, green) of the skeletal muscle fibers.  

Partner with InnoSer for your next DMD study. Consulting with our neurology study experts will allow you to carry out tailored studies while collecting the most study-appropriate data. Contact us to Inquire about Performing a Study in the MDX Mouse Model.