Figure 6. HDAC9 Mutant Mice Are Hypersensitive to Calcineurin-Mediated Hypertrophy.

(A) HDAC9 mutant mice were bred with mice harboring the αMHC-calcineurin transgene (Cn-Tg). Hearts from one-month-old mice of the indicated genotype were isolated (top images), sectioned, and stained with H and E (middle and bottom images). The bottom image shows high magnification images of H and E-stained cardiomyocytes from the ventricular septum. Scale bar equals 2 mm for top and middle, 20 μm for bottom.

(B) Heart weight-to-body weight ratios of mice of the indicated genotypes were determined at four weeks of age. At least ten mice of each genotype were analyzed. Values represent the mean ± standard deviation.

(C) Total RNA was isolated from hearts of mice of the indicated genotype and expression of transcripts for ANF, brain natriuretic peptide (BNP), β-MHC, and GAPDH was determined by Northern blot analysis. The relative abundance of transcripts was quantified and normalized to GAPDH.

(D) Wild-type or HDAC9 mutant mice were crossed to transgenic mice harboring a MEF2-dependent LacZ reporter gene. Offspring were bred with Cn-Tg mice. At least two littermates of each genotype were sacrificed at 8 weeks of age and cardiac MEF2 activity was detected by staining for β-galactosidase activity. Scale bar equals 2 mm.