Simultaneous In Vivo Assessment of Contractile Properties and Electromyographic (EMG) Activities in a Knock-Out Mouse Model of Myotonic Dystrophy

Abstract

Myotonic dystrophy is a dominantly inherited disorder characterized by myotonia and delayed muscle relaxation due to repetitive action potentials in the muscle fibers (hyperexcitability). In this study, a knockout mouse model for the muscle blind proteins (Mbnl1ΔE3∕ΔE3), a valid model for myotonic dystrophy, was assessed, using an in vivo force assessment device, used in conjunction with EMG recording. The aim of the study was to verify whether the muscle force assessment device we developed was capable to sensitively detect the typical characteristics of myotonic muscle. To date, two wild-type and four myotonic female mice have been assessed. After anesthetic induction by isoflurane, the mice were positioned in the apparatus. Hindlimb muscles were stimulated noninvasively by electrodes placed on the muscle of the leg being stimulated. After establishing optimal muscle length, muscle force was assessed after single pulse stimulation at supramaximal voltage followed by double, triple and quadruple pulses. Both legs from each animal were tested and included in the analyses. Muscle force characteristics (peak force, half relaxation time, and area under the force curve (AUC)) and EMG data were recorded and analyzed. Peak forces generated in the myotonic mice were significantly lower (P<0.02), half relaxation times significantly prolonged (P<0.02), and AUCs significantly increased (P<0.002) as compared with the wild-type mice. The recorded EMGs showed characteristic after depolarizations for the myotonic mice. In conclusion, the muscle force assessment device we developed here was able to detect the typical myotonic features in both reproducible and sensitive ways. This device can be considered as a valid tool for future projects concentrating on the in vivo effects of anesthetic agents or therapies on mouse models of myotonia.