Fig. 5: Cardiac pathology of Lmna^F/F:mcm/Sun1^−/− hearts after Cre induction.

A Left ventricular enlargement (LV) was apparent in the Cre-induced (TMX) Lmna^F/F:mcm/Sun1^+/+ (n = 3) hearts but not in the LV of the Cre-induced (TMX) Lmna^F/F:mcm/Sun1^−/− (n = 3) hearts. The Lmna^F/F:mcm/Sun1^+/+ induced (TMX) hearts had significantly increased fibrosis (***P = 0.0001; One-way ANOVA), compared to controls, with no significant fibrosis in the Lmna^F/F:mcm/Sun1^−/− hearts compared to controls (i–iii). The following genotypes served as controls: Lmna^FF:mcm/Sun^+/+ (CTL) (n = 3), Lmna^FF:mcmSun1^−/− (CTL) (n = 3), and Lmna^Wt/Wt:mcm/Sun1^−/− induced (TMX) (n = 4). bar 500 μm, 100 μm (i + ii). B Cardiac papillary muscle active force measurements were significantly reduced from the Cre-induced (TMX) Lmna^F/F:mcm/Sun1^+/+ mice (n = 5) compared to Lmna^F/F:mcm/Sun1^+/+ controls (CTL) (n = 5) (unpaired two-tailed T-test) and Cre-induced (TMX) Lmna^F/F:mcm/Sun1^−/− (n = 3) (**P = 0.0047, *P = 0.0113; unpaired two-tailed T-test). The following genotypes served as controls: Lmna^FF:mcm/Sun1^−/− (CTL) (n = 5), Lmna^FFSun1^−/− induced (TMX) (n = 4), and Lmna^Wt/Wt:mcm/Sun1^−/− induced (TMX) (n = 4). Quantification was performed based on five fibers per animals. A, B Data are presented as mean ± SD. C ECGs were performed up to 28 days after Tmx induction on 3–5-month-old mice. ECGs performed before and after Cre induction revealed a progressive worsening of cardiac contractility in Lmna^F/F:mcm/Sun1^+/+ Cre-induced mice (red line) compared to Lmna^F/F:mcm/Sun1^−/− mice. The loss of Sun1 preserved both EF, FS, and Global Longitudinal Strain (GLS) in Lmna^F/F:mcm/Sun1^−/− hearts compared to Lmna^F/F:mcm/Sun1^+/+ hearts. Echo images were recorded at 28 days after Tmx induction. Data were analysed from the total number of animals per genotype (N) as indicated in the graph. Data are presented as mean ± SD.