JAX performs efficacy studies on mouse models for these diseases: C57BL10.mdx and D2.mdx for DMD, DyW for CMD1A, and A/J for dysferlinopathy. Additional mouse mutants are available for studies.
Efficacy studies performed by JAX® In Vivo Services evaluate muscle function with readouts such as rotarod performance, time to exhaustion with forced exercise, grip strength, and locomotor testing in response to therapeutics. Assessment of inflammation and fibrosis are new offerings to determine amelioration following treatment. Available tests include:
Rotarod tests motor coordination
Open field tests exploration
Force measurement measures the torque of the dorsiflexion of the foot with stimulation
Dye uptake as a measure of muscle fibers damage or fibrosis
Tissue (e.g. skeletal muscles) & blood collection
Cell sorting and quantification on immune cells infiltrating the muscles
Automated morphometry, immunohistochemistry, and detailed histopathology of muscles
Duchenne Muscular Dystrophy (DMD) is one of the most common lethal genetic disease of childhood. It is an inherited X-linked disorder that results in the loss of or aberrant function of dystrophin, a protein involved in maintaining muscle integrity. Onset occurs in infancy and disease phenotypes include muscle weakness, loss of locomotion, and inflammation of the muscles. The following mouse models mimic various aspects of the human disease:
C57BL/10ScSn-Dmdmdx/J(001801) also known as B10.mdx
Congenital Muscular Dystrophy onset occurs at birth. Disease phenotypes include diminished muscle tone and muscle degeneration. The following mouse models mimic various aspects of the human disease:
B6.129S1(Cg)-Lama2tm1Eeng/J (013786), also know as DyW is a model for MDC1A (merosin-deficient congenital muscular dystrophy)
Dysferlinopathy, or Limb-girdle muscular dystrophy type 2B (LGMD2B) onset occurs in young adults. The progressive muscle wasting is variable between patients. The following mouse models mimic various aspects of the human disease:
Hematoxylin & Eosin Stains on dystrophy mouse models
Examples of necrosis and fibers atrophy (top, right), fat infiltration (bottom left) and inflammation (bottom right), hallmarks of the muscle disease in different strains. The pathology of the B10.mdx (top left) is comparatively mild.