Table 1.

SPEG knockin and knockout mouse models

Animal model	Phenotype	Cellular and molecular findings	Ref
Speg germline knockout Deletion of Exons 8-10	Normal baseline in heterozygous knockout but with reduced LV ejection fraction after pressure overload Dilated cardiomyopathy in homozygous knockout 98% death by postnatal day 2 in knockout	Speg expressed in embryonic atria and ventricle Dysregulation of myofibril and sarcomere structure in knockout Reduced cardiac tropomyosin phosphorylation in knockout	9 , 10
Cardiac-specific SPEG conditional knockout SPEGfl/fl (Floxed Exon 9) × αMHC-MerCreMer	Enhanced atrial fibrillation inducibility 2 weeks post-tamoxifen injection Dilated cardiomyopathy and heart failure with reduced fractional shortening and ejection fraction by 8 weeks post-tamoxifen injection Premature death as early as 4 weeks post-tamoxifen injection with 100% death by 24 weeks	T-tubule structure disruption Reduced SR Ca2+ load and steady state Ca2+ transient amplitude Reduced SERCA2a activity and increased RyR2 SR Ca2+ Leak Reduced SPEG mediated JPH2, SERCA2a-T484, and RyR2-S2367 phosphorylation	4 , 11–13
SPEG3A KI mice SPEG-S2461A-S2462A-T2463A knockin	Decreased cardiac ejection fraction Left ventricular dilation	Decreased cardiac SERCA2a activity and oligomerization Reduced SERCA2a-T484 phosphorylation	11
Atrial-specific SPEG conditional knockout SPEGfl/fl (Floxed Exon 9) + AAV9-ANF-Cre	Increased inducibility of atrial fibrillation with rapid atrial pacing	Increased Ca2+ spark frequency in atrial cardiomyocytes Reduced RyR2-S2367 phosphorylation	12