Table 6.
Transgenic murine models associated with long QT syndromes
| Protein/Gene | Genotype | Ion Current | Clinical Condition/Phenotype | Reference Nos. |
|---|---|---|---|---|
| Channel α-subunits: Na+ channel variants | ||||
| Nav1.5/Scn5a | Scn5a-ΔKPQ/+ | INaL | LQTS3; prolonged APD | 416, 843, 1095, 1128, 1129 |
| Scn5a-F1759A | INaL | Atrial and ventricular arrhythmia | 1214 | |
| Scn5a−1798insD/+ | INaL | Overlap syndrome: SND, conduction disease, BrS and LQTS3 | 115 | |
| Channel α-subunits: K+ channel variants | ||||
| Kv4.2/Kcnd2 | Kcnd2-DN | Ito,f | Prolonged APD | 558, 687 |
| Kv1.4/Kcna4 | Kcna4−/− | Ito,s | Normal APD | 558, 687 |
| Kv4.2/Kcnd2 and Kv1.4/Kcna4 | Kv4.2-DN × Kv1.4−/− | Ito,f and Ito,s | Prolonged APD | 558, 687 |
| Kv11.1/Kcnh2 | Merg1−/− | Embryologically lethal | 53, 688 | |
| Merg1+/− | ?IKr | LQTS2; prolonged apical and basal APDs and VERPs | 994 | |
| Merg1b−/− | ?IKr | Normal APD; episodic sinus bradycardia | 627, 1307 | |
| hERG-G628S (dominant negative) expression | ?IKr | Normal QT durations | 53 | |
| Kv7.1/Kcnq1 | Kcnq1−/− | IKs | LQTS1; Jervell and Lange-Nielsen syndrome; prolonged QT intervals in intact animal | 167, 1138, 1222 |
| Human KCNQ1 isoform 2 overexpression | IKs | Prolonged QT interval (dominant negative effects on murine Kcnq1 isoform 1) | 254 | |
| Kv1.5/Kcna5 (ventricular) | Cardiac Kv1.1 NH2-terminal fragment overexpression | Islow | Prolonged QT intervals; spontaneous nonsustained VT | 321, 688 |
| Kv1.5/Kcna5 (atrial) | Kcna5-E375X/+ | IKur | Atrial AP prolongation, EADs, and AF | 853 |
| Kir2.1/Kcnj2 | Kcjn2−/− | IK1, | Anderson-Tawil syndrome (LQTS7); broader APs; spontaneous APs | 1144, 1323 |
| Channel α-subunits: Ca2+ channel variants | ||||
| Cav1.2/Cacna1c. | Cacna1c-G406R/+ | ICaL | LQTS8;Timothy Syndrome (TS) | 56, 192, 277, 1086 |
| Cacna1c-G406R/Akap−/− | Normal phenotype | 192, 1150 | ||
| Channel β-subunits | ||||
| Navβ1/Scn1b | Scn1b−/− | INa and INaL | Human: BrS; mouse: prolonged QT and RR intervals (increased Nav1.5, INa and INaL; altered Ca2+ homeostasis) | 694 |
| Navβ4/Scn4b | Scn4b−/− | INa or INaL | LQTS10; resurgent INa/increased INaL | 373, 713 |
| MinK/Kcne1 | Kcne1−/− | IKs | LQTS5; Jervell and Lange-Nielsen syndrome | 64, 276, 1130, 1195 |
| MirP/Kcne2 | Kcne2−/− | IKslow1, Ito,f | LQT6: prolonged APD | 956 |
| Cytoskeletal proteins | ||||
| Ankyrin-B | Ankyrin-B+/−; ankyrin-B +/E1426G | LQTS4; abnormal Ca2+ homeostasis; triggered events, prolonged QT intervals; VT; atrial arrhythmias | 225, 361, 788, 790 | |
| Ankyrin B−/− | Deficient Kir6.2 membrane expression and decreased IKATP | 182, 649 | ||
| Caveolin-3/Cav3 | Cav3−/− | LQTS9 (transverse tubular abnormalities) | 337, 401, 434, 779 | |