Correction of ClC-1 splicing eliminates chloride channelopathy and myotonia in mouse models of myotonic dystrophy
J. Clin. Invest. Thurman M. Wheeler, et al. 117:3952 doi:10.1172/JCI33355 [Go to this article.]

Figure 3
Antisense morpholino represses splicing of ClC-1 exon 7a. (A) RT-PCR showed reduction of exon 7a inclusion 3 weeks after injection of antisense (anti) morpholino (antisense 1 + antisense 2; 5 μg each) into TA muscle of HSA^LR mice. Pairs of injected TA muscles from each mouse are identified as 1, 2, and 3. Muscle injected with control morpholino (inv) (10 μg) was not different from untreated HSA^LR muscle. HSA^LR and WT mice have the same (FVB) inbred strain background. int, intron, ex, exon. (B) Inclusion of exon 7a remained partially suppressed 8 weeks after injection of antisense morpholino (20 μg antisense 1 vs. 20 μg invert control). (C) ClC-1 antisense morpholino did not correct the misregulated alternative splicing of titin M-line exon 5. The percentage of ClC-1 splice products that include exon 7a is shown at 3 (D) and 8 (E) weeks following morpholino injection. Mean ± SD; n = 3 per group; **P < 0.001; *P = 0.035 antisense versus invert-treated controls; t test. (F) The level of ClC-1 mRNA was increased 3 weeks after treatment with antisense moropholino. ClC-1 mRNA level is expressed in arbitrary units relative to housekeeping gene RNA polymerase II transcription factor IIB. Mean ± SD; n = 3 per group; *P = 0.06 for antisense versus invert-treated control; t test.