Deficiency of selenoprotein S, an endoplasmic reticulum resident oxidoreductase, impairs the contractile function of fast-twitch hindlimb muscles

Selenoprotein S (Seps1) is an endoplasmic reticulum (ER) resident antioxidant implicated in ER stress and inflammation. In human vastus lateralis and mouse hindlimb muscles, Seps1 localization and expression was fiber type specific. In male Seps1+/- heterozygous mice, spontaneous physical activity was reduced compared to wild type littermates (d=1.10, P=0.029). A similar trend also observed in Seps1-/- knockout mice (d=1.12, P=0.051). Whole body metabolism, body composition, extensor digitorum longus (EDL) and soleus mass, and myofibre diameter were unaffected by genotype. However, in isolated fast EDL muscles from Seps1-/- knockout mice, the force frequency curve (1-120 Hz; FFC) was shifted downward versus EDL muscles from wild type littermates (d=0.55, P=0.002), suggestive of reduced strength. During 4 min of intermittent, submaximal (60 Hz) stimulation, the genetic deletion or reduction of Seps1 decreased EDL force production (d=0.52, P<0.001). Furthermore, at the start of the intermittent stimulation ...