Soleus muscle of Down syndrome (Ds) mice does not exhibit impaired contractile function or resistance to fatigue

Abstract

Individuals with Ds perform poorly on tests of neuromuscular strength compared to other individuals, including those with different forms of intellectual disability. Ds individuals also exhibit oxidative stress (OS), which may be the result of triplication and over‐expression of copper‐zinc superoxide dismutase (CuZnSOD) that could play a causative role in the etiology of their muscle dysfunction. A well established mouse model of Ds is the Ts(1716)65Dn (Ts65Dn) which is segmental trisomic for CuZnSOD. Since OS can lead to skeletal muscle contractile dysfunction, we hypothesized that Ts65Dn mice would exhibit impaired muscle force production and resistance to fatigue. We performed muscle contractile measurements on soleus muscles obtained from male Ts65Dn (n=5) mice and wild‐type controls (n=5) using an in vitro preparation. Muscles were stimulated between 1‐300Hz (500‐ms trains; 0.5‐ms pulse) to examine the force frequency response (FFR) and at 40Hz (500‐ms trains; 0.5‐ms pulse) for 5 minutes to study endurance. No difference in the FFR, maximal or submaximal specific tension, endurance, or recovery from fatigue was detected. These findings suggest that Ts65Dn mice do not exhibit skeletal muscle contractile dysfunction, which is in contrast to the human phenotype of DS. We are currently investigating if soleus muscle of Ts65Dn mice exhibits elevated markers of OS. Support: Syracuse University SOE