Table 2.
Characteristics of commonly used mouse models of experimental myocarditis.
| Mouse model | Susceptible mouse strains | Histological characteristic | Clinicopathological characteristic | Advantages and limitations | References |
|---|---|---|---|---|---|
| In vitro-passaged CVB3 or EMCV (103-105 TCID50 or PFU) | BALB/c, A/J, DBA-2, C57BL/6 (4-9 weeks old) | Active myocarditis | Acute myocarditis | (+) use of clinically relevant virus (+) suitable to study CVB3 replication (–) high mortality (–) high biosafety standards required |
(67–82) |
| Heart-passaged CVB3 (103-5x105 PFU) | BALB/c, A/J, C57BL/6 (4-9 weeks old) | Active lymphocytic myocarditis, fibrosis | Acute myocarditis (C57BL/6) and chronic active myocarditis (BALB/c, A/J) | (+) use of clinically relevant virus (+) allows to study disease progression (–) involvement of immune system in CVB3 clearance and autoimmunity (–) high biosafety standards required |
(83–94) |
| Reovirus or MAV-1 (104-107 PFU) | BALB/c, C57BL/6, Swiss (2-7 days old) | Active myocarditis | Acute myocarditis | (+) suitable to study viral replication (+) unique model of pediatric myocarditis (–) clinically irrelevant viruses (–) non-standard methodologies required |
(95–98) |
| T. cruzi infection (50 – 106 trypomastigotes) | BALB/c, A/J, C57BL/6, DBA-2, C3H/He, Swiss (4-12 weeks old) | Active lymphocytic myocarditis, fibrosis | Chronic active myocarditis | (+) use of clinically relevant pathogen (+) recapitulate course of Chagas disease (–) pathogen strain-dependent variability (–) long-term model |
(99–133) |
| Immunization with α-MyHC or troponin I peptide and CFA | BALB/c, A/J, A.SW (6-8 weeks old) | Active/borderline lymphocytic or eosinophilic* myocarditis, fibrosis | Acute myocarditis progressing to DCM | (+) biosafe (+) suitable to study transition from myocarditis to DCM (–) non-physiological disease induction (–) immunization with CFA |
(134–163) |
| Delivery of bmDCs loaded with α-MyHC peptide | BALB/c (6-8 weeks old) | Borderline lymphocytic myocarditis | Acute myocarditis | (+) biosafe (+) suitable to study dendritic cells (–) non-physiological disease induction (–) culture of bmDCs in FCS-rich medium |
(145, 164, 165) |
| TCR-M transgenic mice | BALB/c (≥4 weeks old) | Active/borderline lymphocytic myocarditis | Chronic persistent myocarditis | (+) biosafe (+) suitable to study pathophysiology of heart-specific T cells (–) non-physiological disease induction (–) lack of heart non-specific T cells |
(166) |
| CMy-mOVA mice injected with OT-I CD8+ effector T cells (2.5 × 104-3 × 106) | C57BL/6 (6-20 weeks old) | Active lymphocytic myocarditis | Fulminant myocarditis | (+) biosafe (+) suitable to study T cell-mediated cytotoxicity against cardiomyocytes (–) reactivity against non-cardiac antigen (–) in vitro T cell activation |
(167–170) |
| PD-1/PD-L1-deficiency | BALB/c, MRL (≥4 weeks old) | Active/borderline lymphocytic myocarditis | Fulminant myocarditis | (+) biosafe (+) suitable to study side effects of anti-PD-1/PD-1L therapy (–) multiorgan involvement (–) high mortality |
(171–175) |
| HLA-DQ8 transgenic mice | BALB/c, NOD (≥4 weeks old) | Active/borderline lymphocytic myocarditis | Fulminant myocarditis | (+) biosafe (+) suitable to study cardiac antigen presentation (–) human-mouse chimeric system (–) high mortality |
(176–180) |
α-MyHC, myosin heavy chain α; bmDCs, bone marrow-derived dendritic cells; CFA, complete Freund's adjuvant; CMy-mOVA - cardiac myocyte restricted membrane-bound ovalbumin; CVB3, coxsackievirus B3; EMCV, encephalomyocarditis virus; FCS, fetal calf serum; HLA, human leukocyte antigen; MAV-1, murine adenovirus type 1; OT-I, major histocompatibility complex class I-restricted ovalbumin-specific; PD-1, programmed cell death protein-1; PD-L1, PD-1 ligand; PFU, plaque forming unit; TCID50, 50% tissue culture infectious dose; TCR-M, T cell receptor (TCR) specific to α-MyHC.
*
in Ifng−/−Il17a−/− BALB/c mice.