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. 2013 Jan 15;21(3):602–609. doi: 10.1038/mt.2012.264

Figure 5.

Figure 5

Exon skipping induces LDL reduction in transgenic human APOB mice. Transgenic human APOB mice were injected with weekly doses of 20 mg/kg SSOs as indicated over 8 weeks, and blood samples were taken 2 weeks before the first injection and 3 days after the 3rd, 6th, and 8th injections. Animals were killed 3 days after the last injection, and liver tissue samples were taken for RNA extraction and subsequent RT-qPCR. (a) Skipping efficiencies: SSO 14-53P (6.76 ± 3.55%; n = 9), SSO sc14-53P (scrambled control; 0.34 ± 0.08%; n = 6), untreated control group (UT; 0.25 ± 0.03%; n = 6), and 0.25 mg/ml pravastatin in water ad libitum (statin; 0.25 ± 0.02%; n = 6). (b) Quantification of APOB26–27 (27 inc), APOB26–28 (skip), APOB25–26 (total), and mouse Apob (ms) in SSO 14-53P treated mice relative to untreated and SSO 14-53P controls, presented as whisker plots as in Figure 4d. (c) Baseline-corrected reduction in ΔLDL values presented. The percentage change in LDL cholesterol was calculated for each mouse at each timepoint using the following formula: 100% × (LDLtimepoint − LDLbaseline)/LDLbaseline. The mean of these percentage changes for the placebo groups (SSO sc14-53P serving as control for 14-53P; untreated group serving as control for the pravastatin group) was calculated as the expected baseline change for LDL cholesterol. This baseline change was then subtracted from the percentage changes observed for the experimental groups (SSO 14-53P and pravastatin): week 3 SSO 14-53P (black; −51.08 ± 19.37%) and pravastatin (gray; −13.02 ± 13.88%), week 6 SSO 14-53P (−33.50 ± 23.11%) and pravastatin (−4.35 ± 5.50%), and week 8 SSO 14-53P (−34.44 ± 11.81%) and pravastatin (−2.86 ± 9.38%). LDL, low-density lipoprotein; RT-qPCR, reverse transcriptase-quantitative polymerase chain reaction; SSO, splice-switching oligonucleotides.