Table 1 Cardiac phenotypes in genetically engineered mouse model related to mtDNA-induced inflammation
GenesType of genetically engineeringExperimental modelCardiac phenotypeCytokine or chemokine induction in heart
mtDNA sensors
 TLR9KOTACIncreased cardiac function and survivalDecreased in IL-6 [84]
KOMINo changeNo change [97]
 Inflammasomes
  NLRP3KOI/RNo changeDecreased in TNF-α [100]
KOI/RWorseningDecreased in TNF-α [99]
  Caspase1KOI/RProtectionNot described [98]
TG (CA)LPS challengeDecreased cardiac function and survivalIncreased in IL-1β [104]
  ASCKOI/RProtectionDecreased in TNF-α, IL-1β, IL-6 [98]
KOI/RWorseningNot significantly changed [99]
 cGAS/STING pathway
  cGASKOMIImproved function and survivalDecreased in chemokine CXCL10 [96]
  STINGKOMINo changeDecreased in chemokine CXCL10 [96]
  IRF3KOMIImproved function and survivalDecreased [96]
KOTACExacerbation of cardiac hypertrophyNot described [105]
Cardio-specific TGAortic bandingAttenuation of cardiac hypertrophyNot described [105]
Genes potentially involved in mtDNA-induced inflammatory responses
  TFAMTGMIImproved function and heart failureNot described [86]
TGVolume overloadImproved functionNot described [87]
  CypDKOMIProtectionNot described [119]
KOTACWorsening functionNot described [120]
KOI/RProtectionNot described [88,89]
  DNaseIICardio-specific KOTACWorsening functionIncreased in IL-6 [84]

Cardiac phonotypes characterized in genetically engineered mouse models are listed. Abbreviations: ASC: apoptosis-associated speck-like protein containing a caspase activation and recruitment domain; CA: constitutive active; cGAS: cyclic GMP–AMP synthetase; CXCL10: chemokine (C-X-C motif) ligand 10; CypD: cyclophilin D; IL: interleukin; I/R: ischemia/reperfusion; IRF3: interferon regulatory factor 3; KO: knockout mice; MI: myocardial infarction; NLRP3: nucleotide oligomerization domain-like receptor family pyrin domain containing 3; STING: stimulator of interferon genes; TAC: transverse aortic constriction; TFAM: transcription factor A, mitochondrial; TLR9: Toll-like receptor 9; TNF: tumour necrosis factor.