1. CBFβ deficiency leads to heart failure in zebrafish.
CBFβ deficiency leads to heart failure in zebrafish. (A,B,D,E) MO2-cbfβ-injected embryos develop pericardial edema and precardial blood congestion owing to disturbed cardiac contractility. Lateral view and magnification of control-injected (MO-control; A,B) and MO2-cbfβ-injected (D,E) embryos at 72 hpf (v, ventricle; a, atrium; asterisk, pericardial edema). In MO-control- and MO2-cbfβ-injected embryos, the atrium and ventricle are separated by the atrio-ventricular ring (B,E). (C,F) Atrial- and ventricle-specific myosin heavy chains are expressed normally, also implicating normal molecular chamber specification [green, antibody against atrial-specific myosin (S46-AB); red, antibody against ventricular and atrial myosin (MF20-AB)]. (G) After injection of MO2-cbfβ, 95% of the morphants develop heart failure. (G, inset) cDNA analysis of CBFβ morphants after injection of the MO2-cbfβ splice-morpholino reveals skipping of exon 2 (band at 167 bp) or integration of intron 1 (band at 861 bp). The wild-type form of cbfβ (band at 254 bp) is severely reduced in the CBFβ-knockdown zebrafish. (H) Bar graphs representing end-systolic (ESD) and end-diastolic (EDD) ventricular diameters of MO-control- and MO1-cbfβ-injected embryos at 60 hpf. In CBFβ morphants, end-systolic ventricular chamber diameters are significantly enlarged (P<0.05). (I,J) Anti-CBFβ immunofluorescence stainings of skeletal muscle (skm) of MO-control-injected (I) and MO1-cbfβ-injected (J) embryos showing reduced CBFβ expression after knockdown of CBFβ.
Benjamin Meder et al. J Cell Sci 2010;123:
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