Table 2.

Summary of transgenic models, phenotypes, and effects of SUMOylation (nuclear events)

Molecule	Transgenic model	Model characteristics	Phenotypes and the effect of SUMOylation
XBP-1	Xbp-1−/− [108,173]	Homozygous embryonically lethal	Cellular necrosis of cardiac myocytes [108]. Hypoplasmic fetal livers, resulting in death from anemia via reducing hematopoiesis [173]. Spliced XBP-1 SUMOylation inhibits transcriptional activity of XBP-1s and subsequent UPR target gene expression [109].
PPARs	Pparα−/− [110–112] Cardiac specific Pparγ−/− [114] Cardiac specific Pparδ−/− [113]	Non-lethal Non-lethal Non-lethal	Decreased cardiac fatty acid oxidation rates, while glucose oxidation rates and reliance on glucose metabolism for ATP production are increased [110–112]. Progressive cardiac hypertrophy with mitochondrial oxidative damage, and most mice died from dilated cardiomyopathy [114]. Reduced expression of key fatty acid oxidation genes and also reduced basal myocardial fatty acid oxidation. Progressive myocardial accumulation, cardiac hypertrophy, and congestive heart failure [113]. PPARα and γ SUMOylation inhibits PPARα and γ transcriptional activity [115,116]. PPARδ SUMOylation promotes its degradation and inhibits PPARδ transcriptional activity [117].
ERK5	Erk5−/− Cardiac-specific Erk5−/−	Embryonically lethal Cardiac-specific ERK5 KO flox mice under α-MHC promoter No cardiac abnormalities in morphology or function up to 6 months of age	Loss of vascular integrity with EC misalignment and leakage due to defects in angiogenesis [174] Attenuates cardiac hypertrophy remodeling with accelerated cardiac apoptosis and dysfunction after TAC [120] Reduces CHIP Ub ligase activity and increased ICER post-MI[132] ERK5 SUMOylation inhibits ERK5 transcriptional activity [121].
CHIP	Chip−/−	Non-lethal	Increases infarct size via up-regulating apoptosis after ischemia and reperfusion [131].
HDAC1 and 2	Hdac1−/− [175] Hdac2−/− [175]	Homozygous embryonically lethal Survival until the perinatal period	Obliteration of the lumen of the right ventricle, excessive hyperplasia, apoptosis of cardiomyocytes, and bradycardia [175]. HDAC1 SUMOylation promotes HDAC1 stability and upregulates its expression and activity [145]. HDAC2 SUMOylation increases p53 de-acetylation and promotes NF-κB activation [146].