Figure 6. Dox-induced shut-off of the β2a transgene prevents disease.

(A) Gross morphological pictures of high-expressing DTG β2a mice without Dox treatment (No Dox; induced) or with Dox (shut off) at 14 weeks of age. (B) Heart weight normalized to body weight and (C) fractional shortening in high-expressing DTG mice without Dox or with Dox. Numbers indicate the number of mice analyzed in each group. *P < 0.05 versus DTG without Dox, Student’s t test. (D) Kaplan-Meier curves of control tTA single-transgenic and low-expressing DTG mice infused with Iso at 60 mg/kg/d for 14 days or with PBS vehicle. Low-expressing DTG mice were given Dox for 2 weeks prior to shut off β2a expression. (E) Fractional shortening in control tTA single-transgenic and low-expressing DTG mice pretreated with Dox for 2 weeks; some were given 14 days of Iso treatment. Numbers indicate the number of mice analyzed in each group. Data were analyzed by ANOVA. (F) Histological assessment of cardiac ventricular pathology by Masson’s trichrome in control tTA single-transgenic and low-expressing DTG mice with PBS or Iso infusion for 14 days with 2 weeks of prior Dox treatment. (G) Histological assessment of Ca²⁺ deposits in myocytes by von Kossa staining in control tTA single-transgenic and low-expressing DTG mice with PBS or Iso infusion for 14 days with 2 weeks of prior Dox treatment.