Phenotypes associated with this allele

• Allele Symbol: Kcnj8^tm1Sse
• Allele Name: targeted mutation 1, Susumu Seino
• Allele ID: MGI:2180015
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Kcnj8^tm1Sse/Kcnj8^tm1Sse	involves: 129S1/Sv * 129X1/SvJ	MGI:6236325
hm2	Kcnj8^tm1Sse/Kcnj8^tm1Sse	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3041531

Genotype
MGI:6236325

hm1

• Allelic Composition: Kcnj8^tm1Sse/Kcnj8^tm1Sse
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

cardiovascular system

hypertension ( J:202037 )

• mice exhibit an increase in blood pressure

abnormal vascular smooth muscle physiology ( J:202037 )

• no measurable K(ATP) currents are seen in vascular smooth muscle cells from mesenteric arteries

muscle

abnormal vascular smooth muscle physiology ( J:202037 )

• no measurable K(ATP) currents are seen in vascular smooth muscle cells from mesenteric arteries

Genotype
MGI:3041531

hm2

• Allelic Composition: Kcnj8^tm1Sse/Kcnj8^tm1Sse
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:76195 )

• 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

cardiovascular system phenotype ( J:76195 )

N • electrophysiological measurements of ventricular myocytes exhibited no abnormalities in the plasma membrane of homozygous null cardiomyocytes relative to wild-type

N • in addition, flavoprotein oxidation measurements revealed normal plasma membrane ATP-sensitive K+ current channels in homozygous null cardiomyocytes

irregular heartbeat ( J:76195 )

• representative ECGs generated by radio telemetry revealed spontaneous ST elevations and atrioventricular blocks of various degrees in homozygous null mice

abnormal myocardial fiber physiology ( J:76195 )

• 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

coronary artery spasm ( J:76195 )

• 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