Extended Data Fig. 5: Allele specific knockdown of variant SPTLC1 mRNA.
From: Childhood amyotrophic lateral sclerosis caused by excess sphingolipid synthesis
a, The two allele-specific siRNAs targeting the L39del and F40_S41del alleles do not reduce SPTLC1 mRNA levels in control cells at concentrations as high as 100nM. Error bars are SEM. Four replicates were performed. b, Sphingolipidomic analysis of patient derived fibroblasts with SPTLC1 ALS variants (F40_S41del and two patient lines with L39del) after treatment with 10 nM allele-specific siRNA targeting each corresponding variant were analysed and compared to control fibroblasts. Following the knockdown, the cells were labeled with D3,15N-L-serine and D4-L-alanine. The de novo synthesized +3 ceramide and sphingomyelin levels show a reduction in patient cells when treated with variant-specific siRNAs. Error bars are SEM. Three replicates were performed.
