Table 4.
Murine variants recapitulating conduction abnormality
| Gene/Protein | Genotype | Phenotype | Reference Nos. |
|---|---|---|---|
| Na+ channel Nav1.5 (α-subunits) | |||
| Scn5a/Nav1.5; Na+ channel α-subunit | Scn5a+/− | BrS including fibrotic conduction changes | 734, 867, 1095 |
| Scn5a-1798insD | Overlap BrS/LQT3 syndrome | 208, 939, 1184 | |
| Serine of Nav1.5 SIV motif replaced by premature stop codon causing truncated ΔSIV | Loss of binding to PDZ domain of lateral membrane α1-syntrophin; reduced lateral membrane NaV1.5 and INa | 1063 | |
| Na+ channel Navβ (β-subunits) | |||
| Scn2b/Navβ2; Na+ channel, intercalated disk, β2-subunit | Scnb2−/− | Seizures; reduced neuronal Na+ channel density; cardiac phenotypes not yet examined. | 185 |
| Scn3b/Navβ3; Na+ channel, transverse tubular, β2-subunit | Scn3b−/− | Reduced Na+ channel function; monomorphic or polymorphic VT on programmed stimulation | 304, 402, 403, 452, 713 |
| Na+ channel-associated proteins | |||
| Ankyrin-G (affecting intercalated disk Nav1.5 and and spectrin) | Cardiac-selective ankyrin-G−/− | Reduced INa; altered AP waveform; bradycardia; reduced ventricular (QRS) conduction; ventricular arrhythmias following Na+ channel antagonism | 716, 787, 790, 889, 1006 |
| Synapse-associated protein-97 (SAP97) (affecting intercalated disk Nav1.5) | αMHC-Cre/Sap97-fl/fl: cardiomyocyte-specific SAP97 deletion | Reduced IK1, Ito, IKur; intact INa; slightly increased Nav1.5 expression | 355 |
| Desmosomal proteins | |||
| Plakophilin-2 | Pkp2+/− | Desmosomal abnormalities; reduced and modified INa; ventricular arrhythmias | 173, 174 |
| Desmoglein-2 | Dsg2-N271S | Reduced INa and conduction velocities | 952. |
| Kv4.3 channel mediating Ito | |||
| Semaphorin 3a (Sema3a). | Sema3a−/− (KO of naturally occurring protein inhibitor of Kv4.3 (underlies Ito) | Arrhythmic BrS-like phenotype | 130, 476 |
Note: For desmosomal proteins, see also Table 8.