Fig. 2: Generation of a cardiac-specific Ptrh2-knockout (CKO) mouse induces PPCM with heart failure postpartum.

a Ptrh2 mRNA levels in wildtype Ptrh2^flox/flox non-transgenic (Ptrh2-NT) control female mice (Never Pregnant vs. Pregnant; n = 4 biologically independent LV samples/group; p = 0.017 or Pregnant vs. PostPartum; n = 4 biologically independent LV samples/group; p < 0.0167). b Ptrh2 LV immunoblot from Ptrh2-NT control female mice; Never Pregnant, Pregnant and Post Partum. Quantification performed in triplicate normalized to Never Pregnant Gapdh levels. n = 4 biologically independent LV samples/group. Statistical test (a) Two-way ANOVA with Tukey’s multiple comparison. Error bars are mean± s.e.m. (b) Two-tailed unpaired t-test. Error bars are mean± s.e.m. c–e Survival curves (%; α-Mhc-Cre^+/-, Ptrh2-NT, and Ptrh2-CKO) in (c) Never pregnant. n = 20 biologically independent mice/genotype/group), (d) Pregnant, or (e) Postpartum groups. d, e n = 60 biologically independent mice/genotype/group. f Echocardiography M-mode images and EKGs (inset) from Ptrh2-NT_NP versus Ptrh2-CKO_NP or Ptrh2-NT_PP versus Ptrh2-CKO_PP mice. g–j Echocardiography measurements: % LV Fractional Shortening (g; LVFS; p < 0.0001), Ejection Fraction (h; LVEF; p < 0.0001), Internal Diameter at End-Diastolic (i; LVIDd; p = 0.0236), and Internal Diameter at End-Systole (j; LVIDs; p = 0.0001) between Ptrh2-NT versus Ptrh2-CKO Never Pregnant or Postpartum groups. n = 8 biologically independent mice/genotype/group. k Heart/body weight (HW/BW; (p < 0.0001)) or (l) Heart weight/tibia length (HW/TL; p < 0.0001) ratios. n = 11 biologically independent mice/genotype/group. m Cardiomyocyte cross-sectional area. n = 3 biologically independent mice/group (p = 0.006). n Ptrh2-NT and Ptrh2-CKO NP (left) or PP (right) gross hearts (first row, scale bar, 5000 μm); H&E stained LV sections (second row: longitudinal; third row: cross-sectional, scale bar, 1000 μm; fourth row, scale bar, 50 μm), WGA (fifth row; scale bar, 100 μm), PSR (sixth row: interstitial; seventh row perivascular, scale bar, 50 μm), n = 3 biologically independent mice/genotype/group. o Hydroxyproline quantitation of Ptrh2-NT versus Ptrh2-CKO from NP or PP groups. n = 6 biologically independent mice/group, p < 0.0001. p–q LV mRNA expression of Col 3a1(p = 0.001) and CCN2 (p = 0.001) in Ptrh2-NT, Ptrh2-CKO NP and PP groups. n = 7 biologically independent mice/genotype/group. Statistical test (g–q) Two-Way ANOVA with Tukey’s multiple comparison. Error bars are mean± s.e.m. Each dot represents an independent biological sample. Source data are provided as a Source Data file. See Supplementary Fig. 2.