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. 2016 Jun 16;1(9):e85904. doi: 10.1172/jci.insight.85904

Figure 1. Cardiac expression of CITED4 produces physiological cardiac hypertrophy.

Figure 1

(A) Western blot demonstrating CITED4 from whole-heart lysates after 3 weeks of expression by removal of doxycycline (Doxy) in transgenic mice expressing tTA and CITED4-FLAG. (B) Quantification of CITED4 expression as compared with control mice in iCITED4 without doxycycline (3.04- ± 0.63-fold) or with doxycycline (1.13- ± 0.13-fold); n = 4 mice per group, *P < 0.05 by 1-way ANOVA for serial comparisons. (C) Restricted cardiac expression of CITED4-Flag in the double-positive (tTA+/CITED4+) transgenics as demonstrated by Western blot from lysates from multiple tissues. (D) Gross and microscopic histology of representative samples, including H&E (left panels) and MTS for fibrosis (right panels). Scale bars: 50 μm. (E) Increases in heart weight to tibial length for males (8.36 ± 0.35 mg/mm vs. 6.84 ± 0.32 mg/mm) and for females (6.62 ± 0.22 mg/mm vs. 5.72 ± 0.08 mg/mm). n = at least 5 animals per group. (F) Fractional shortening before and after induction of iCITED4 for 3 weeks and 6 weeks, respectively; n = 8–12 males per group. (G) Increase in relative mass index after 3 weeks of induction in CITED4 transgenics remains stable for at least 6 weeks of expression. Relative increase in LV mass for CITED4 transgenics as compared with controls: 27.7% ± 5.2% at 3 weeks and 25.1% ± 7% at 6 weeks. For all graphs: significance determined by the Student’s t test unless otherwise specified; *P < 0.05, **P < 0.01.