Heart disease is a complex and heterogeneous disease. Notably, studies have demonstrated gender differences in the expression and types of cardiovascular disease, such as dilated cardiomyopathy (DCM), a major underlying cause of heart failure. Previously we showed that loss of A-Kinase Anchoring Protein 13 (Akap13), a unique proto-oncogene and estrogen receptor modulator, resulted in enlarged embryonic hearts, defective cardiac sarcomere formation, and embryonic lethality in mice. Data have also shown cAMP-dependent Protein Kinase A (PKA) to be involved in DCM pathophysiology. Given the established role of AKAP13 in cell signaling, its ability to bind and modulate ligand-activated nuclear hormone receptors and transcription factors, and its association with actin and other cytoskeletal components, we hypothesized that a functional AKAP13 protein was required for cardiomyocyte function in the adult heart; defective function of AKAP13 could promote DCM. To this end, we established an inducible, cardiac-specific Akap13 conditional knockout (Akap13cKO) mouse model using a Cre-lox recombination strategy with two separate Cre-recombinase expressing mouse models (α-MHC-MerCreMer and Tnnt2-rtTA; TetO-Cre).
Cardiac functional examination of Akap13cKO mice revealed significant biventricular dilated cardiomyopathy with compensatory hypertrophic remodeling of the left ventricle and left atrial enlargement, decreased left and right ventricular systolic function, and abnormal left ventricular diastolic function. Of note, female Akap13cKO mice displayed a more pronounced cardiac phenotype and were more likely to die post-recombination.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-6136 |
| Date | 01 January 2016 |
| Creators | Baig-Ward, Kimberlyn M |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © Kimberlyn Maravet Baig-Ward |
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