Fibrotic change |
TGF-β1
|
Cardiac-specific TGF-β1 overexpression (MHC-TGFcys33 ser) |
Atrial fibrosis and AF inducibility |
1193 |
TNF-α |
Cardiac-specific TNF-α overexpression |
Atrial dilation, fibrosis, thrombosis, spontaneous AF in ambulant mice |
598, 974
|
Angiotensin I converting enzyme (ACE) |
ACE 8/8 |
Atrial dilatation, fibrosis, and spontaneous AF in ambulant mice |
1280 |
|
Cardiac-specific overexpression of ACE |
|
|
Adenosine (A1 or A3) receptors |
Cardiac-specific A3AR overexpression of at high (A3high) or low (A3low) adenosine levels |
Bradycardiomyopathy |
300 |
Ras homolog gene family member A (RHOA) |
Cardiac-specific (αMhc promoter) overexpression of WT or activated form of RHOA |
Atrial enlargement, cellular hypertrophy, interstitial fibrosis, AF susceptibility, atrioventricular block, premature death |
991 |
Mitogen-activated protein kinase kinase 4 (Mkk4), |
Atrial cardiomyocyte-specific conditional knock-out Mkk4-acko-Nppa-Cre4
|
AF, atrial fibrosis, upregulated TGF-β1 signaling and dysregulation of matrix metalloproteinases |
245 |
Hypertrophic cardiomyopathy (HCM) |
α-Myosin heavy chain (Myh6) |
Mhc-R403Q/+ |
QT dispersion, conduction heterogeneity, inducible VT, sudden death, variable degree of hypertrophy |
112, 347, 1266
|
Myosin binding protein C (Mybp-C3) |
MyBP-C-t/+ and MyBP-C-t/t; (t = truncated Mybp-C3)
|
Hypertrophy, fibrosis, ventricular ectopic activity |
113 |
Troponin T (Tnnt2) |
Severity: Tnnt2-I79N >TnnT-F110I>TnnT-R278C |
Altered Ca2+ sensitivity, spontaneous VT, reduced IK1 |
83, 580, 583
|
Myosin light chain (coded by Mlc17) |
Mlc-17-M149V |
Hypertrophy |
1185 |
Ras (HRAS) |
Targeted, chronic Ras-Raf–MAPK pathway activation and αMHC-loxp-GFP-loxp-H-RasV12 |
Hypertrophy, ventricular arrhythmia, atrial fibrillation, conduction block |
969, 1346
|
Dilated cardiomyopathy (DCM): sarcomeric protein mutations |
α-Myosin heavy chain (Myh6) |
Mhc-F764L/+, Mhc-S532P/+, Mhc-F764L/F764L and Mhc-S532P/S532P) |
Dilatation |
1018 |
Mammalian-enabled protein and vasodilator-stimulated phosphoprotein (Vasp) |
Cardiac myocyte-restricted, α-myosin heavy chain promoter-directed expression of the dominant-negative VASP-EVH1 domain |
Dilatation, hypertrophy, bradycardia, sudden death |
293 |
Neuron-restrictive silencer factor (Nsrf) |
α-MHC-dnNRSF (dominant-negative knock-in) |
Dilatation, heart block, sudden death |
608 |
Dilated cardiomyopathy (DCM): cytoskeletal protein mutations |
Lamin (coded by LMNA) |
LMNA+/− |
AV nodal disease, atrial arrhythmia, VT |
1267 |
|
Lmna-N195K |
Dilatation, fibrosis bradycardia, SA node exit block |
807 |
|
Lmna-H222P/H222P |
Models Emery-Dreifuss syndrome; dilatation, increased PR interval, variable conduction block, QRS prolongation, ventricular extrasystoles |
45 |
Dilated cardiomyopathy (DCM): SR Ca2+-cycling protein mutation |
Phospholamban (Pln) |
Pln-R14Del |
Dilation, fibrosis, VT sudden death |
397 |
|
Pln-R9C/R9C |
Reduced protein kinase A activity, delayed SERCA-Ca2+ reuptake, dilated cardiomyopathy, congestive heart failure |
1019 |
Dilated cardiomyopathy (DCM): developmental gene mutations |
Cardiac homeobox gene product (Nkx-2.5) |
Ventricle-restricted deficiency: Nkx2-5-f/f/cre+
|
Hypertrabeculation, noncompaction, conduction disturbance |
871 |
Vinculin (VCL) |
Cardiac-restricted Vclfl/fl MLC-2vCre/+ knockout |
Dilatation, VT, sudden death |
1324 |
Troponin I (TNNI3) |
cTnI-R192H |
Atrial dilatation, decreased LV volume, decreased EF, delayed relaxation |
278, 279
|
Arrhythmogenic right ventricular dysplasia (ARVD): desmosomal protein gene mutations |
Plakophilin-2 (Pkp2) |
Pkp2−/− |
Lethal |
376 |
|
Pkp2+/− |
Normal cardiac phenotype |
376 |
Plakoglobin (Pg) |
Pg−/− |
Lethal |
647 |
|
Cardiac specific Pgf/f-αMHCcre |
RV enlargement, fibrosis, slowed RV conduction, spontaneous VT of right ventricular origin. Phenotype exacerbated by training |
571, 647, 973
|
Desmoplakin (Dsp) |
Dsp−/− |
Embryonic lethal |
339, 475
|
|
Dsp+/− |
Slowed conduction and inducible VT prior to adult structural changes |
366 |
|
Cardiac overexpression of flag-tagged Dsp cDNA carrying Dsp-R2834H-Tg COOH-terminal mutation |
Apoptosis, fibrosis, RV and LV dilatation, reduced ventricular function, widened intercalated disks |
1296 |
|
Cardiac specific Dsp-f/f- (MLC2v-Cre)
|
Cardiomyopathic changes, ventricular arrhythmias accentuated by exercise and catecholaminergic challenge, slowed RV conduction |
706 |
Desmoglein (Dsg2) |
Cardiac overexpression of flag-tagged dominant Dsg2-N271S mutant (homologous with human DSG2–N266S ARVC mutation) |
Myocyte necrosis, calcification and fibrous tissue replacement, spontaneous ventricular arrhythmias, conduction slowing, ventricular dilatation and aneurysms, replacement fibrosis and SCD |
896 |
Arrhythmogenic right ventricular dysplasia (ARVD): laminin receptor mutations |
Laminin receptor 1 (Lamr1) |
KK/Rvd (knock-down) |
Right ventricular fibrosis, QRS prolongation |
48 |
Left ventricular noncompaction cardiomyopathy (LVNC) |
Cypher/Zasp |
Mutations in Cypher/Zasp |
LVNC with DCM and HCM phenotype, early postnatal death |
1345, 1350
|