Fig. 2: Cardiomyocyte-specific overexpression of Thbs1 induces lethal cardiac atrophy.
From: Thbs1 induces lethal cardiac atrophy through PERK-ATF4 regulated autophagy
a Low magnification images of tTA cont. and Thbs1 DTG whole mount cardiac histological sections stained with Masson’s trichrome at 6 weeks of age. Scale bar is 2 mm. b Ventricular weight-to-body weight (VW/BW) ratio at the indicated time points in tTA cont. and Thbs1 DTG mice. P-values are shown in the graph. c Echocardiography measured fractional shortening (FS) percentage in the two groups of mice at 6–7 weeks (w) of age. *P = 0.0007 vs tTA cont. d Pulmonary edema was analyzed by lung weight-to-body weight (LW/BW) ratios in the indicated groups of mice at 7 weeks of age. *P = 0.0231 vs tTA cont. e Kaplan–Meier survival plot of tTA cont. and Thbs1 DTG animals with continuous Thbs1 expression (never Dox; P < 0.0001 vs tTA cont.). f Experimental regimen of early Dox administration to inhibit Thbs1 transgene expression during embryonic and early postnatal development in Thbs1 DTG animals (Dox was removed at 3w of age). g Kaplan–Meier survival plot of tTA cont. and Thbs1 DTG mice treated with Dox as shown in panel “f” (P < 0.0001 vs tTA cont.). h VW/BW ratio and i FS percentage at 24 weeks of age given the treatment regimen shown in panel “f”. *P = 0.0073 vs tTA cont. for “h” and *P = 0.0039 vs tTA cont. for “i”. j Schematic diagram for administration of Dox beginning at 3 weeks of age to shut down Thbs1 expression thereafter (Dox was given at 3w and beyond). k Representative Western blots of protein extracts from hearts of Thbs1 DTG mice at 8 weeks of age in Thbs1 DTG mice as shown in panel “j”, assayed for Thbs1, BiP, and Gapdh as a loading control. l VW/BW ratio and m FS percentage at 24 weeks of age in the mice treated as shown in panel “j”. The number of biologically independent animals analyzed is indicated on each graph. Statistical analysis was performed using two-tailed Student’s t test (b–d, h, i, l, m), or survival analysis by two-tailed log-rank test (e, g). Error bars are ±standard error of the mean. Source data are provided as a Source Data File.
