Skeletal muscle weakness in osteogenesis imperfecta mice

Area of Science:

• Biochemistry
• Genetics
• Physiology

Background:

• Osteogenesis imperfecta (OI) is a heritable connective tissue disorder characterized by bone fragility.
• Patients with OI frequently report exercise intolerance, muscle fatigue, and weakness, which are poorly understood.
• OI is caused by mutations in collagen genes or proteins involved in collagen post-translational modification.

Purpose of the Study:

• To investigate inherent muscle pathology in mouse models of osteogenesis imperfecta (OI).
• To evaluate muscle weight, fiber characteristics, collagen content, and muscle force in OI mice.
• To determine if skeletal muscle pathology contributes to muscle weakness in OI.

Main Methods:

• Examined soleus, plantaris, gastrocnemius, tibialis anterior, and quadriceps muscles from mild (+/oim) and moderately severe (oim/oim) OI mice.
• Assessed muscle weight, fiber cross-sectional area (CSA), fiber type, histomorphology, and fibrillar collagen content.
• Measured absolute, relative, and specific peak tetanic force (P(o), P(o)/mg, P(o)/CSA) for individual muscles.

Main Results:

• Oim/oim mouse muscles were smaller, had less fibrillar collagen, and exhibited decreased peak tetanic force (P(o)).
• Oim/oim muscles showed an inability to sustain P(o) over the testing duration.
• +/oim mice displayed a milder skeletal muscle phenotype with less severe weakness compared to oim/oim mice.

Conclusions:

• Muscle weakness in oim mice is linked to inherent skeletal muscle pathology.
• OI mouse models demonstrate significant muscle deficits, including reduced size and force.
• The findings highlight the contribution of muscle pathology to the clinical presentation of OI.