Table 1.
Genotype-Phenotype Correlation in Genetically-Modified Mice with Altered KATP channel Function
| Mouse genotype | KATP function | Early Death | Coronary spasm | Hypertension | Heart rate | Arhythmias | Major phenotypes | Citation |
|---|---|---|---|---|---|---|---|---|
| Whole-animal | ||||||||
| Kir6.2−/− | Loss-of-function in striated muscle, neurons and β-cell | No | No | ↔ | ↔ | No | Insulin secretion impaired, Impaired cardiac and skeletal muscle stress response. Increased glucose uptake in sk. muscle, Increased exercise-induced fiber damage | (240, 250, 274, 275, 391, 392, 393, 400, 461) |
| Kir6.1−/− | Loss-of-function in vascular smooth muscle | Yes | Yes | ↔ | ↔ | Yes | Coronary-vasospasm and premature death | (276) |
| SUR2−/− | Loss-of-function in all muscle | Yes | Yes | ↑ | ↔ | Yes | Coronary-vasospasm and premature death, resistant to ischemia-reperfusion damage. Increased glucose uptake in sk. Muscle. | (54, 55) |
| SUR1−/− | Loss-of-function in atrial muscle, neurons, and β-cell | No | No | ↔ | n.d. | No | Insulin secretion impaired, Loss of atrial KATP channels, Resistant to ischemia-reperfusion damage | (112, 371) |
| CMV-SUR2A | Gain-of-function in cardiac muscle | No | No | n.d. | n.d. | n.d. | Resistant to ischemic damage | (93) |
| Cardiac-specific transgene | ||||||||
| αMHC-Kir6.2[ΔN30,K185Q] | Reduced ATP-sensitivity and current density in cardiac muscle | No | n.d. | n.d. | ↓ | No | Remodeling of E-C coupling, ↑ ICa,, ischemic preconditioning abolished | (111, 219) |
| αMHC-FLAG-SUR1 | Reduced current density in heart | No | n.d. | n.d. | n.d. | Yes | PR prolongation | (113, 114) |
| αMHC-FLAG-SUR2A | Reduced current density in heart | No | n.d. | n.d. | n.d. | No | No significant physiological effect | (114) |
| αMHC-Kir6.2[ΔN30, K185Q] × αMHC-FLAG-SUR1 | Reduced ATP-sensitivity and current density in cardiac muscle | Yes | n.d. | n.d. | n.d | Yes | Constellation of arrhythmias and premature death | (113) |
| αMHC- Kir6.2[ΔN30, K185Q] × αMHC-FLAG-SUR2A | Reduced ATP-sensitivity and current density in cardiac muscle | No | n.d. | n.d. | n.d | No | No significant physiological effect | (113) |
| αMHC-Kir6.1-AAA | Dominant-negative suppression in cardiac muscle | Yes | n.d. | n.d. | ↑ | No | APD prolongation, Premature death | (405) |
| αMHC-Kir6.2-AAA | Dominant-negative suppression in cardiac muscle | Yes | n.d. | n.d. | ↔ | No | APD prolongation, Premature death | (405) |
| Vascular-specific transgene | ||||||||
| SM22-SUR2B/SUR2−/− | Smooth muscle-restored expression in SUR2−/− mice | Yes | Yes | n.d. | ↔ | Yes | Coronary-vasospasm and premature death | (199) |
| Tek-Kir6.1-AAA | Dominant-negative suppression of endothelial KATP | No | Yes | n.d. | n.d. | n.d. | (260) | |