Table 2.
List of the current animal models used in MCM.
| Animal | Mutations | Cardiological Phenotype | Clinical Manifestations | Year | Ref |
|---|---|---|---|---|---|
| Mice | Ant1 | mitochondrial myopathy/MCM | ragged-red muscle fibers, dramatic proliferation of mitochondria, cardiac hypertrophy with mitochondrial proliferation, severe defects in coupled respiration, metabolic acidosis, exercise intolerance. | 1997 | [21] |
| Mice | Ant1 | DMC | substantial myocardial hypertrophy/ventricular dilation, cardiac function declining in early age, LV circumferential, radial, rotational mechanics reduced, myocyte hypertrophy, fibrosis, calcification. | 2011 | [22] |
| Mice | MRPS34 | progressive cardiomyopathy | fractional shortening of the heart, pronounced liver dysfunction, inhibition of mitochondrial translation, decreased oxygen consumption and respiratory complex activity. | 2015 | [23] |
| Mice | Med30zg | MCM/cardiac failure | changes in transcription of cardiac genes for OXPHOS and mitochondrial integrity precipitous lethality 2–3 weeks after weaning. | 2011 | [24] |
| Mice | Ndufs6 | CI deficiency-specific MCM | LV systolic function, cardiac output, and functional work capacity markedly reduced, at increased risk of cardiac failure and death after 4 months in males and 8 in females, ATP synthesis decreased, hydroxyacylcarnitine increased. | 2012 | [25] |
| Mice | TFAM | progressive, lethal DCM | elevated ROS production, activated DNA damage response pathway, decreased cardiomyocyte proliferation. | 2018 | [26] |
| Mice | TFAM | MCM | critical enzymes in fatty acid oxidation show decreased expression, glycolytic enzymes show increased expression. | 2004 | [27] |
| Mice | CHCHD10-S55L | MCM | typical ISRmt, mitochondrial architecture and function altered in the heart, metabolic pathway changed from oxidative to glycolytic. | 2022 | [28] |
| Mice | CHCHD2/CHCHD10 | MCM | C2/C10 DKO mice have disrupted mitochondrial cristae, cleavage of the l-OPA1, activation of the ISRmt and development of cardiomyopathy. | 2020 | [29] |
| Rat | Isca1 | MMDS with cardiomyopathy; MCM | Isca1 HET rats exhibit thin-walled ventricles, larger chambers, cardiac dysfunction and myocardium fibrosis, damaged mitochondrial morphology, enzyme activity and ATP production. | 2021 | [30] |
| Dog | QIL1 | MCM | cristae abnormalities and cardiac arrhythmias, hyperplastic mitochondrial, cristae rearrangement, electron dense inclusions, lipid bodies in muscle. | 2019 | [31] |
| Zebrafish | ndufa7/hhatla | HCM | cardiac functional defects, associated with increased expression of pathological hypertrophy biomarkers ANP and BNP. | 2020 | [32] |
| Mongolian gerbils | iron overload | Iron-overload cardiomyopathy | cardiac hypertrophy, increased cardiac output, and normal exercise tolerance at shorter durations, concentric cardiac hypertrophy, cardiac output and exercise capacity were impaired at longer duration. | 2002 | [33] |
| Mice | FXN | FRDA- cardiomyopathy | impaired mitochondrial OXPHOS, bioenergetics imbalance, deficit of Fe-S cluster enzymes and mitochondrial iron overload, recapitulated most features of FRDA cardiomyopathy. | 2014 | [34] |
| Mice | Bcs1lp.S78G | MCM | GRACILE syndrome, growth failure, progressive hepatopathy and kidney tubulopathy, | 2019 | [35] |
| Mice | TAZ | BTHS cardiomyopathy | significantly enlarged hearts, ventricular. dilation at 16-weeks of age, lower total CL concentration, abnormal CL fatty acyl composition. | 2021 | [36] |
| Mice | C1QBP | MCM | increased oxidative stress, embryonic lethality with the embryonic fibroblast, cardiomyocyte dysfunction. | 2017 | [37] |
| Mice | Crif1 | MCM | mice suffered from progressive hypertrophy and died from heart failure; mutant mice died within 2 weeks postnatal, showing cardiac hypertrophy associated with mitochondrial dysfunction. | 2013 | [38] |
Abbreviations: ANT1, adenine nucleotide translocase 1; ANP, atrial natriuretic peptide; ATP, adenosine triphosphate; BNP, plasma brain natriuretic peptide; BTHS, Bartters syndrome; CHCHD, coiled-helix-coiled-helix; CL, cardiolipin; C1QBP, Complement component 1 Q subcomponent-binding protein; DCM, dilated cardiomyopathy; FRDA, Friedreich’s ataxia; FXN, frataxin gene; HCM, hypertrophic cardiomyopathy; ISRmt, mitochondrial integrated stress response; LV, left ventricle; MCM, mitochondrial cardiomyopathy; MMDS, multiple mitochondrial dysfunction syndromes; MRPS34, mitochondrial ribosomal protein of the small subunit 34; OPA1, mitochondrial dynamin like GTPase; OXPHOS, oxidative phosphorylation; ROS, reactive oxygen species; TAZ, tafazzin; TFAM: mitochondrial transcription factor A.