Fig. 3.

KLF15 deficiency severely exacerbates DMD, and KLF15 is required for therapeutic efficacy of GCs. qRT-PCR of KLF15 from (A) vastus lateralis biopsies of human subjects with DMD versus healthy controls (n = 10) and (B) quadriceps tissue of mdx versus control mice (n = 5; *P < 0.05 for indicated comparisons). (C) GSEA demonstrating that genes reduced in mdx skeletal muscle tissue (curated from ref. 44) are highly enriched for those regulated by the GC–KLF15 axis. (D) Survival by genotype of male offspring generated from crosses between Klf15^+/− mdx males and females. There is significant postnatal death of Klf15^−/− mdx males (P < 0.05; n = 157 total mice). (E) Plasma CPK concentration from mice of indicated genotypes (n = 6–7; *P < 0.05 for indicated comparison). (F) Representative H&E-stained section of hindlimb muscle tissue from mice of indicated genotypes before death (age P4–5; representative of n = 3). (Scale bar, 20 µm.) (G) Schematic of experimental design for GC therapeutic trial (± prednisolone 5 mg/kg·dose oral gavage given 3 times weekly). (H) Klf15 expression in quadriceps (n = 4–7; *P < 0.05 for indicated comparisons). (I) Treadmill endurance exercise capacity (n = 6–15), (J) wire-hang endurance assay (n = 6–13), and (K) grip strength (n = 6–11) of indicated genotypes treated ± prednisolone (*P < 0.05 for indicated comparisons). (L) Plasma CPK concentration (n = 6–9; *P < 0.05 for indicated comparisons). (M) Representative H&E-stained sections of quadriceps from mice of indicated genotypes and treatments (representative of n = 3). (Scale bar, 100 µm). Data are shown as mean ± SEM.