Figure 1

Muscle weakness in muscle from Smn^-/-; SMN2 mice. (A) TA muscle preparations from P5 Smn^-/-;SMN2 mice and control littermates were used to assess tetanic and twitch force normalized to the muscle cross-sectional area. P5 Smn^-/-;SMN2 TA muscles produce significantly less twitch force than control littermates. (B) Reduction in normalized maximal peak tetanic force in P5 Smn^-/-;SMN2 TA muscle compared with controls. (C) Administration of tubocurarine to block NMJs did not influence relative force production in Smn^-/-;SMN2 muscles. In five independent experiments, Smn^-/-;SMN2 mice produced less force than controls following treatment with tubocurarine. (D) Similar relative force decreases in Smn^-/-;SMN2 and control mice during fatigue elicited with one tetanic contraction every second for 3 min. Peak tetanic forces are expressed as a percentage of the pre-fatigue force. (E) Unstimulated force occurred when muscles failed to relax between contractions and is expressed as a percentage of the pre-fatigue peak tetanic force. During a fatigue protocol, P5 Smn^-/-;SMN2 TA muscles show increased unstimulated force compared with controls. (F) Unstimulated force appeared much sooner in Smn^-/-;SMN2 TA muscles than in controls. NMJ, neuromuscular junction; TA, tibialis anterior; N = 5 or 6; *, P < 0.05.