Table 1
Cardiac phenotypes of genetically modified PGC-1/ERR animal models.
| Genetic Model | Comments | Cardiac Phenotype | References |
|---|---|---|---|
| PGC-1α KO | 1) Disruption of PGC-1 by insertion of additional exon 3 between exons 5-6. | 1) Mild bradycardia, blunted heart rate response to dobutamine, reduced myocardial FAO capacity, slightly reduced expression of mitochondrial and FAO genes, reduced ATP generation, increased expression of PGC-1β. | 31, 32 |
| 2) Disruption of PGC-1α gene by deletion of exons 3-5. | 2) Blunted contractile response to dobutamine infusion in Langendorff ex vivo heart, reduced cardiac function with aging or pressure overload, reduced ATP generation slightly reduced expression of mitochondrial and FAO genes. | 29, 30, 48 | |
| PGC-1β KO | 4 independent KO/KD mouse models generated | Mild bradycardia, blunted heart response to dobutamine, reduced ATP generation, slightly reduced expression of mitochondrial genes in heart and skeletal muscle, increased expression of PGC- 1α. | 28, 33–35 |
| PGC-1α/β DKO | PGC-1α global KO mice crossed with a cardiac- specific KO of PGC-1β | Arrest in cardiac perinatal mitochondrial biogenesis, marked reduction in cardiac mitochondria, death from heart failure in first day of life. | 28 |
| ERRα KO | Global knockout | Increased expression of PGC-1α and ERRγ, heart failure after aortic banding; reduction of cardiac ATP/energy reserves. | 39, 43 |
| ERRγ KO | Global knockout | Increased expression of PGC-1α and ERRα, absent mitochondrial biogenesis after birth, QT prolongation on ECG, early mortality | 38 |
| PGC-1α OE | PGC-1α expression driven by MHC promoter | Uncontrolled mitochondrial proliferation, severe cardiomyopathy and death from heart failure | 8 |
| PGC-1α COE | Tetracycline inducible double transgenic mouse using MHC-rtTA and TRE- PGC-1α | Increased expression of mitochondrial genes, modest mitochondrial biogenesis, dilated cardiomyopathy within 2 weeks of PGC-1α induction (reversible) | 36 |
KO (knockout), KD (knockdown), DKO (double knockout), OE (overexpression), COE (conditional overexpression), TAC (transaortic constriction), rtTA (tetracycline transactivator), TRE (tetracycline response element)