TABLE 2.

Overview of in vivo studies of CaMKIIδ splice variant overexpression in cardiomyocytes.

Splicevariant	Mouse model	Intervention/Cardiac Phenotype	Ca2+ handling/Major signaling	References
CaMKIIδA	Cardiomyocyte specific transgenic overexpression (αMHC-driven)	•Cardiac hypertrophy at 4 weeks of age •Contraction defects •Death at 8 weeks of age	•Ca2+ handling defects	Xu et al., 2005
	Cardiomyocyte specific transgenic overexpression (αMHC-driven)	•Activation of hypertrophic gene program at 4 weeks of age •Cardiac hypertrophy and moderate cardiac dysfunction at 4 months of age	•Downregulation of PLN phosphorylation (Ser16/Thr17) •Decrease in SR Ca2+ uptake (in vitro) •Repression of HDAC4 and upregulation of MEF2 activity •Increase in PP2A activity	Zhang et al., 2002, 2007
CaMKIIδB	AAV9-mediated overexpression in cardiomyocytes in CaMKIIδ/γ (αMHC-driven) KO background	•Protection against myocardial damage and dysfunction following 1 hour ex vivoI/R	-	Weinreuter et al., 2014
	Cardiomyocyte specific transgenic overexpression (αMHC-driven) in cardiomyocytes (αMHC-driven) CaMKIIδ KO background	•Cardiac damage not affected after I/R injury for 1 day	•Upregulation of IL-6 mRNA	Gray et al., 2017
	Cardiomyocyte specific transgenic (αMHC-driven)	•Cardiac hypertrophy at 6 weeks of age •Heart failure at 12 weeks of age	•Ca2+ handling defects •Repression of HDAC4 and upregulation of MEF2 activity	Maier et al., 2003; Zhang et al., 2003, 2007; Ljubojevic-Holzer et al., 2020
	AAV9-mediated overexpression in cardiomyocytes in CaMKIIδ/γ (αMHC-driven) KO background	•Cardiac damage not affected after I/R injury for 1 day	-	Weinreuter et al., 2014
CaMKIIδC	Cardiomyocyte specific transgenic overexpression (αMHC-driven) in cardiomyocyte (αMHC-driven) CaMKIIδ KO background	•Exacerbated myocardial damage and dysfunction following 1 hour ex vivoI/R	•Upregulation of IKK-α/β phosphorylation and NF-κB protein content •Upregulation of TNF-α and IL-6 mRNA	Gray et al., 2017
	Cardiomyocyte specific transgenic (αMHC-driven) plus mitochondrial localization signal	•Modest cardiac hypertrophy (Without cardiomyocyte cross-sectional area changes) •Dilated cardiomyopathy	•MCU phosphorylation •Decrease in ATP content •Decreased mitochondrial complex I and increased complex II activity	Luczak et al., 2020
CaMKIIδ9	Cardiomyocyte specific transgenic (αMHC-driven)	•Cardiac hypertrophy at 6 weeks of age •Heart failure at 10 weeks of age	•Disruption of UBE2T-dependent DNA repair pathway •DNA damage	Zhang et al., 2019