Analysis Tools
mortality/aging
|
• homozygous null mice died prematurely between 5 and 6 weeks after birth due to myocardial ischemia
• homozygous mutant mice were found dead within 24 hours of displaying normal behavior and activity levels ("sudden cardiac death")
|
cardiovascular system
| N |
• electrophysiological measurements of ventricular myocytes exhibited no abnormalities in the plasma membrane of homozygous null cardiomyocytes relative to wild-type
• in addition, flavoprotein oxidation measurements revealed normal plasma membrane ATP-sensitive K+ current channels in homozygous null cardiomyocytes
|
|
• representative ECGs generated by radio telemetry revealed spontaneous ST elevations and atrioventricular blocks of various degrees in homozygous null mice
|
|
• in contrast to the normal electrophysiological properties of homozygous null cardiomyocytes, vascular smooth-muscle KATP channels were defective in mutant aortas
• homozygous null aortic smooth-muscle cells failed to generate a vasodilation response to pinacidil (a K+ channel opener) both in vivo (blood pressure decrease) and in vitro (vasorelaxation of aortic rings), indicating dysregulation of the vascular tonus
• administration of the ergot alkaloid methylergometrine, a vasoconstrictive agent, elicited ST elevation followed by cardiac death in mutant mice but not in wild-type mice, resulting in hypercontractility of coronary arteries and a phenotype similar to Prinzmetal (or variant) angina in humans
|
|
• some homozygous null mice exhibited spontaneous coronary spasm under basal conditions
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| coronary artery disease | DOID:3393 |
OMIM:300464 OMIM:607339 OMIM:608316 OMIM:608318 OMIM:608320 OMIM:610947 OMIM:611139 OMIM:612030 OMIM:614293 |
J:76195 | |
