Objective: Characterize the motor phenotype and contractile force characteristics of skeletal plantar flexor muscles in a mutant mouse model for spasticity. This model displays a spontaneous mutation in glycine receptor affecting muscle function.

Background: Spasticity is a medical condition characterized by motor abnormalities, caused by striatal muscle hyperactivity. In adults, spasticity develops in patients suffering from multiple sclerosis, traumatic brain injury, spinal cord injury or stroke, whereas in children, it is commonly associated with cerebral palsy. Development of novel treatments for spasticity has been impacted by relative sparsity of animal models for this condition.

Method: Homozygous spastic mice , males and females, and their wildtype controls were tested in a battery of behavioral tests at different ages (neurological score, righting test, grip-strength, rotarod, catwalk, spontaneous behavior). At the end of the behavioral assessment contractile properties of Gastrocnemius medialis (GM) and Soleus (Sol) muscles were analyzed in situ, followed by their morphological and histological characterization.

Results: There were significant differences between motor phenotypes of spastic mice and their wild-type controls. Spastic mice were consistently lighter in body weight and weaker in motor phenotype when compared to wildtype controls at each age. The gait of spastic mice was characterized by “hopping” with periodic tremors during walking. Indeed, objective gait analyses identified short footprint length (tiptoe walking), short hind leg stride length (hopping) in spastic mice. In situ muscle force assessment showed that spastic mice have weaker Sol and GM muscles, but these differences were reflective of smaller muscle mass observed in Glrbspa mice. Fiber cross sectional areas were decreased in both Sol and GM spastic muscles. GM and Sol in spastic mice displayed a fast to slow fibers transition, which was related to a lower rate of force development and higher fatigue resistance.

Conclusion: We identified multiple motor features and striatal muscle alterations that differed significantly between spastic mice and wildtype controls. Some of these features resembles those observed in spastic patients. Additional experiments, involving anti-spastic medication are needed to assess predictive validity of the model.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/characterization-of-the-motor-phenotype-and-striatal-muscle-analysis-in-a-mouse-model-of-hereditary-spasticity/