FIGURE

Fig. 9

ID

ZDB-FIG-200306-57

Publication

Lee et al., 2020 - REEP5 depletion causes sarco-endoplasmic reticulum vacuolization and cardiac functional defects

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Fig. 9

In vivo AAV9-mediated REEP5 depletion in mice results in increased cardiac fibrosis, activated cardiac ER stress, cardiac dysfunction, and death.

a Immunoblot analysis of AAV9-mediated REEP5 depletion in mice 4 weeks post viral infection. b Histological analyses of AAV9 Scram shRNA and REEP5 shRNA injected mouse hearts at 4 weeks post viral infection. Top panels: H&E, bottom panels: Masson’s trichrome stain. Scale, 20 μm. All images shown are representative of approximately 20 total images captured per condition, n = 3 independent biological replicates. c Transmission electron microscopy analysis of AAV9 REEP5 shRNA-injected myocardium reveals degeneration of muscle fibers and disrupted SR membranes and organization compared to scram controls. M mitochondria, SR sarcoplasmic reticulum, V vacuoles. Scale, 0.5 nm. All images shown are representative of approximately 20 total images captured per condition, n = 3 independent biological replicates. d In vivo echocardiographic heart function assessment of AAV9 scram and AAV9 REEP5 shRNA-injected mice at 4 weeks post viral infection, n = 5. e Echocardiographic M-mode and B-mode measurements showed significantly compromised cardiac function with reduced cardiac ejection fraction and cardiac output, n = 5 independent biological replicates. Asterisks indicate a statistically significant p value in a Tukey’s multiple comparison analysis where ***p < 0.001; data are presented as mean ± SEM. f Immunoblotting analysis of cardiac ER stress markers (GRp78, GRp94, XBP1, ATF4, and CHOP) and ER-dependent apoptosis (caspase 12) upon AAV9-induced REEP5 depletion in vivo in mice, n = 3; p values are shown. g Immunoblots of RTN4, ATL3, and CKAP4 upon AAV9-induced REEP5 depletion in vivo in mice, n = 3 independent biological replicates. Source data containing original uncropped immunoblots are provided as a Source Data file.

Expression Data

Expression Detail

Antibody Labeling

Phenotype Data

Phenotype Detail

Acknowledgments

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