| First Author | Myers VD | Year | 2018 |
| Journal | J Cell Physiol | Volume | 233 |
| Issue | 9 | Pages | 6319-6326 |
| PubMed ID | 29323723 | Mgi Jnum | J:264044 |
| Mgi Id | MGI:6192826 | Doi | 10.1002/jcp.26482 |
| Citation | Myers VD, et al. (2018) Haplo-insufficiency of Bcl2-associated athanogene 3 in mice results in progressive left ventricular dysfunction, beta-adrenergic insensitivity, and increased apoptosis. J Cell Physiol 233(9):6319-6326 |
| abstractText | 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 (BAG3(fl/+) ). Mice were crossed with alpha-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(-/-) BAG3(fl/+) ). 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 ([Ca(2+) ]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. |
