Transcriptome (left) and proteome (right) of WT and iSMNKO QUAD: principal-component analysis (PCA), differentially expressed genes/proteins, and heatmaps of transcripts/proteins showing meanZscores. Data are presented as mean values SEM. For transcriptomics and proteomics data, statistical significance was tested by unpaired two-tailed Student’s t test, gene expression and protein abundances are presented as logFC (fold change) of KO over WT, andpvalues are FDR-adjusted using Benjamini-Hochberg method. For targeted metabolomics data, two-way ANOVA with Holm-Šídák post hoc test was used (genotype effect,*p< 0.05,**p< 0.01,****p< 0.0001; running effect,#p< 0.05,##p< 0.01,###p< 0.001,####p< 0.0001). Mice were male and 15–20 weeks of age.