Figure 4. Effect of AAV-mediated TAZ replacement therapy on neonatal survival of TAZ-KO mice.

A. Schematic of AAV-hTAZ, and scAAV-hTAZ. Luciferase-expressing AAV was used as control virus (AAV-Ctrl). B. Experimental design. Neonatal TAZ-KO mice were treated at P1. Survival to weaning (P28) was the primary endpoint, and echocardiography and histological parameters were secondary endpoints. C. Viral transduction of cardiac and skeletal muscle was evaluated 7 days after AAV injection by in situ hybridization using probes specific to hTAZ (green puncta) and cardiomyocyte marker Actn2 (blue). D. Survival curve of mice after treatment with AAV at P1. Bars, standard error. P-values, comparison to TAZ-KO treated with AAV-Ctrl. Using Bonferonni correction for 3 comparisons, the significance threshold is p=0.0167. E-F. Serial echocardiography. Treated mice were not distinguishable from WT until 4 months, when the treatment groups showed reduced systolic function. G. Myocardial sections stained by fast green/sirius red. Bar=200 μm. H. Quantification of fibrosis. I. MLCL/CL in P7 skeletal muscle. D: Mantel-Cox. E, F: Repeated measures two way ANOVA followed by Tukey’s post hoc test. H, I: one-way ANOVA with Tukey post-hoc testing.