Probucol ameliorates renal and metabolic sequelae of primary CoQ deficiency in Pdss2 mutant mice. Mus musculus

To discern whether the same transcriptional signature of mitochondrial dysfunction previously reported in B6.Alb/cre,Pdss2loxP/loxP liver-conditional knockout mice (Peng, Falk et al. PLoS Genetics, 2008 [PMID 18437205]) was present regardless of Pdss2 mutation type, as well as to assess whether pharmacologic therapies modulate expression of particular pathways, genome-wide transcriptional profiling was performed in liver from B6.Pdss2(kd/kd) missense mutant mice on standard chow or supplemented long-term with either probucol or CoQ10. Overall design: For analysis of lifelong probucol and CoQ10 supplementation effects in B6.Pdss2(kd/kd) missense mutant mice, total RNA was isolated from the livers of B6 mice and from Pdss2(kd/kd) missense mutant mice fed a normal diet, or a diet supplemented with Probucol or CoQ10. Total RNA was individually hybridized to 20 total Illumina Mouse WG-6 v2.0 arrays, which included 5 biological replicates from each of the 4 groupings: untreated B6.Pdss2(kd/kd) missense mutant mice, probucol-treated B6.Pdss2(kd/kd) mice, CoQ10-treated B6.Pdss2(kd/kd) mice, and untreated B6 wild-type mice. Total RNA