Fig. 6: SMN loss in skeletal muscle causes autophagy dysregulation.
a Pie chart of differentially expressed genes belonging the 6 main groups of the autophagic list [57] in Smn1ΔSkm myofibers. The percentages indicate the proportion of the genes differentially expressed in Smn1ΔSkm myofibers over the number of genes belonging to each category as defined in [57]. b Heat map of expression levels of genes related to autophagy activation and lysosomal biogenesis. Each column corresponds to a single myofiber of the indicated genotype. The dendrogram cluster myofibers with similar transcriptional signature. c, d Equal amounts of gastrocnemius muscle lysates (20 µg) were separated by SDS-PAGE and immunoblotted using the indicated antibodies. Each lane corresponds to an individual mouse of the indicated genotypes. Densitometry analysis yielded the following values: SMN: 1.16 ± 0.14 in Wt (n = 4) and 0.77 ± 0.04 in Smn1ΔSkm (n = 5), p = 0.02; LC3II: 0.04 ± 0.01 in Wt (n = 4) and 0.11 ± 0.02 in Smn1ΔSkm (n = 5), p = 0.03; PINK: 0.79 ± 0.14 in Wt (n = 4) and 1.6 ± 0.29 in Smn1ΔSkm (n = 4), p = 0.04; PARKIN: 0.14 ± 0.02 in Wt (n = 4) and 0.8 ± 0.17 in Smn1ΔSkm (n = 4), p = 0.01 p-eIF2α/ eIF2αː 0.19 ± 0.02 in Wt (n = 4) and 0.4 ± 0.05 in Smn1ΔSkm (n = 4), p = 0.01; LAMP2 Wt 0.79 ± 0.11 in Wt (n = 5) and 0.48 ± 0.03 in Smn1ΔSkm (n = 7), p = 0.013; and LAMP1: 0.75 ± 0.14 in Wt (n = 6) and 0.37 ± 0.06 in Smn1ΔSkm (n = 6), p = 0.037.
