DEV015818 Supplementary Material

Files in this Data Supplement:

• Supplemental Figure S1 -

  Fig. S1. Normal muscle fiber regeneration. Degeneration was induced in the gastrocnemius muscles of 8- to 12-week-old wild-type (A,C,E,G) and Tln1HSA-CREko (B,D,F,H) mice via the injection of cardiotoxin. No major difference in the rate of regeneration was observed between Tln1HSA-CREko mice and control mice. Five days after injection, necrotic fibers (A,B, arrows) and small regenerating myofibers with centrally located nuclei (C,D, arrowheads) were observed. At 10 days, fibers with centrally located nuclei were present (E,F, arrows). In both mutant and control mice, the architecture of myofibers was largely reconstituted by 21 days after toxin injection (G,H). Scale bars: 100 µm in A,D; 50 µm in E-H.

• Supplemental Figure S2 -

  Fig. S2. EBD uptake following exercise. Muscles isolated from mice subjected to exercise were evaluated for EBD incorporation via bright field illumination. No significant dye uptake was observed in wild-type (A,C) or mutant (B,D) diaphragm or gastrocnemius muscles. Mild dye uptake was observed only in the gastrocnemius muscle of one mutant (E) and in the hind limb muscles of one mutant (G), but not in other mutant animals (F) (n=5).

• Supplemental Figure S3 -

  Fig. S3. Peak stresses and work generated by Tln1-deficient muscle. (A) In an eccentric contraction protocol, the peak stresses exerted by muscles isolated from 2-month-old Tln1HSA-CREko mice were comparable to controls. (B) By contrast, muscle from 7-month-old Tln1HSA-CREko showed a significant reduction in peak isometric stress at each eccentric contraction cycle, except the first one, where more variation was observed. (D) The workload of 7-month-old Tln1HSA-CREko mice during each eccentric contraction was reduced compared with controls. By contrast, at 2 months no significant difference was observed between mutant and control muscle (C). Work was normalized against muscle mass. n&γτ;4 per genotype/time point; mean ±s.e.