Fig. 5: Pex5 deletion in skeletal muscle results in early-onset muscle weakness, preceding muscle atrophy.

A Biological Processes (BP) and Cellular Components (CC) inhibited at 3mo. The Enrichment Score of each term is plotted. B Heatmap of 12 muscle contraction-related genes significantly inhibited in KO vs Ctrl GNM muscles at 3mo. C Amino acids concentration in GNM muscles from 3mo mice. Each dot represents a single muscle analyzed (Ctrl n = 4; KO n = 7). D Normalized force–frequency curve of Ctrl and KO mice at 3 and 18mo. Data shown as mean ± SEM. E Normalized maximal tetanic force. D, E Each dot represents a single muscle analyzed (3mo: Ctrl n = 7; KO n = 13; 18mo: Ctrl n = 6; KO n = 8). Fiber size distribution of control and KO TA muscle at 3 (F), 9 (G), and 18mo (H). Data shown as mean ± SEM in columns. 3mo: n = 4 Ctrl, n = 3 KO (F); 9mo: n = 7 Ctrl, n = 7 KO mice (G); 18mo: n = 6 Ctrl/KO mice (H). G p-value a = 0.0058, b = 0.0044, c = 0.0028. H p-value a = 0.0085, b = 0.0013, c = 0.0329, d = 0.0279, e = 0.0288, f = 0.0118. I mRNA levels of atrophy-related genes in TA muscle of 9mo control and KO mice. Left: ubiquitin-proteasome-related genes; middle: autophagy-related genes; right: ER stress-related genes. Each dot represents a single muscle (Ctrl n = 6; KO n = 5). J Fbxl22 mRNA levels in TA muscles at 3, 9, and 18 months. Each dot represents a single muscle (3mo: Ctrl n = 4; KO n = 7; 9mo: Ctrl n = 6; KO n = 5; 18mo: Ctrl n = 6, KO n = 7). K Running distance until exhaustion of Ctrl and KO mice at 3 and 18 months. Each dot represents a single mouse (3mo: Ctrl n = 5; KO n = 3; 18mo: Ctrl n = 5; KO n = 7). 3mo, 9mo and 18mo refer to samples from 3-, 9-, and 18-month-old mice. Unpaired two-sided Welch’s t tests (C, E lower panel, J), Mann–Whitney test (E upper panel), or multiple unpaired two-sided Welch’s t test (F–I) used when comparing two groups. A two-way ANOVA with Sidak’s multiple comparisons test performed when comparing more than two groups (K). Source data are provided as a source data file.