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• W2784068865 abstract "Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid protein that is found predominantly in the heart, skeletal muscle, and many cancers. Deletions and truncations in BAG3 that result in haplo-insufficiency have been associated with the development of dilated cardiomyopathy. To study the cellular and molecular events attributable to BAG3 haplo-insufficiency we generated a mouse in which one allele of BAG3 was flanked by loxP recombination sites (BAG3fl/+). Mice were crossed with α-MHC-Cre mice in order to generate mice with cardiac-specific haplo-insufficiency (cBAG3+/−) and underwent bi–weekly echocardiography to assess their cardiac phenotype. By 10 weeks of age, cBAG3+/− mice demonstrated increased heart size and diminished left ventricular ejection fraction when compared with non-transgenic littermates (Cre−/−BAG3fl/+). Contractility in adult myocytes isolated from cBAG3+/− mice were similar to those isolated from control mice at baseline, but showed a significantly decreased response to adrenergic stimulation. Intracellular calcium ([Ca2+]i) transient amplitudes in myocytes isolated from cBAG3+/− mice were also similar to myocytes isolated from control mice at baseline but were significantly lower than myocytes from control mice in their response to isoproterenol. BAG3 haplo-insufficiency was also associated with decreased autophagy flux and increased apoptosis. Taken together, these results suggest that mice in which BAG3 has been deleted from a single allele provide a model that mirrors the biology seen in patients with heart failure and BAG3 haplo-insufficiency." @default.
• W2784068865 created "2018-01-26" @default.
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• W2784068865 date "2018-03-30" @default.
• W2784068865 modified "2023-10-10" @default.
• W2784068865 title "Haplo‐insufficiency of Bcl2‐associated athanogene 3 in mice results in progressive left ventricular dysfunction, β‐adrenergic insensitivity, and increased apoptosis" @default.
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• W2784068865 doi "https://doi.org/10.1002/jcp.26482" @default.
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