Fig. 3.

Colchicine treatment selectively reduces HSA transgene mRNA levels and partially rescues missplicing in the HSA^LR DM1 mouse model. (A and B) Effect of colchicine treatment (0.4 mg/kg) or PBS (control) for 14 d by i.p. injection on HSA transgene mRNA levels (A) or endogenous Dmpk levels (normalized to Gtf2b) (B) (n = 6 age- and gender-matched littermates in each treatment group, mean ± SD). ****P < 0.0001. (C) MA plot displaying gene-expression differences comparing colchicine-treated to PBS control-treated mice. Gene-expression change (log2 fold) is plotted against the mean of normalized counts. Red points represent changes with adjusted P < 0.1. (D) Heat map displaying the rescue of alternative cassette exon inclusion by mean normalized PSI identified from the top 100 missplicing events (top 50 cassette inclusion and top 50 exclusion events) in HSA^LR mice treated with colchicine compared to HSA^LR mice treated with PBS (control) and wild-type mice (P < 0.0005, FDR < 0.05). (E) RT-PCR isoform analysis of the indicated alternative cassette exon events following treatment with PBS-control or colchicine (mean, n = 6). ***P < 0.001. (F) Immunofluorescence against Clcn1 protein in colchicine-treated and PBS control-treated HSA^LR mouse quadricep muscle sections. DAPI staining for nuclei is shown in blue.