Phenotypes associated with this allele

• Allele Symbol: Kcnj8^em1Nich
• Allele Name: endonuclease-mediated mutation 1, Colin G Nichols
• Allele ID: MGI:6389009
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Kcnj8^em1Nich/Kcnj8^em1Nich	involves: C57BL/6J * CBA/J	MGI:6389014
ht2	Kcnj8^em1Nich/Kcnj8^+	involves: C57BL/6J * CBA/J	MGI:6389011
cx3	Abcc9^em1Nich/Abcc9^+ Kcnj8^em1Nich/Kcnj8^+	involves: C57BL/6J * CBA/J	MGI:6389026

Genotype
MGI:6389014

hm1

• Allelic Composition: Kcnj8^em1Nich/Kcnj8^em1Nich
• Genetic Background: involves: C57BL/6J * CBA/J

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

mortality/aging

premature death ( J:281903 )

• survival is drastically decreased, with mice dying within a week or so after weaning

growth/size/body

weight loss ( J:281903 )

• mice lose weight prior to dying

digestive/alimentary system

abnormal intestine morphology ( J:281903 )

• distended intestines

Genotype
MGI:6389011

ht2

• Allelic Composition: Kcnj8^em1Nich/Kcnj8⁺
• Genetic Background: involves: C57BL/6J * CBA/J

mortality/aging

decreased survivor rate ( J:281903 )

• minor decrease in survival

premature death ( J:281903 )

• minor decrease in survival

cardiovascular system

abnormal aorta morphology ( J:281903 )

• increase in aortic diameters, ranging from 15% to 70% increases around the proximal aorta

aortic arch dilation ( J:281903 )

increased myocardial fiber size ( J:281903 )

• ventricular myocyte hypertrophy

enlarged heart ( J:281903 )

• cardiomegaly results from cellular hypertrophy

increased heart weight ( J:281903 )

• 1.7-fold increase in heart weight

cardiac hypertrophy ( J:281903 )

abnormal heart left ventricle morphology ( J:281903 )

• approximate 2-fold increase in left ventricle mass

aortic valve stenosis ( J:281903 )

• 4 of 5 mice show aortic stenosis

dilated heart left ventricle ( J:281903 )

increased cardiac output ( J:281903 )

• cardiac output is about 65% higher

abnormal heart echocardiography feature ( J:281903 )

• echocardiography shows an approximate 2-fold increase in left ventricle mass, dilated left ventricle chamber diameters with increases in left ventricle posterior wall and intraventricular septal thickness, increased cardiac output, increased rate of left ventricle emptying

• however, relative wall thickness and fractional shortening are not different

aortic valve regurgitation ( J:281903 )

• 4 of 5 mice show aortic insufficiency

hypotension ( J:281903 )

• anesthetized 3-month old mice show a reduction of both systolic and diastolic basal blood pressures

• the effect of pinacidil administration on blood pressure is severely blunted

• approximate 30-mmHg decreases in blood pressure at both night and day, although the difference is not significant during the daytime

abnormal vascular smooth muscle physiology ( J:281903 )

• enhanced basal K(ATP) conductance in vascular smooth muscle

increased vasodilation ( J:281903 )

• carotid arterial diameters across a full range of physiological pressures are increased, indicating dilated, compliant arterial vessels

muscle

increased myocardial fiber size ( J:281903 )

• ventricular myocyte hypertrophy

abnormal vascular smooth muscle physiology ( J:281903 )

• enhanced basal K(ATP) conductance in vascular smooth muscle

increased vasodilation ( J:281903 )

• carotid arterial diameters across a full range of physiological pressures are increased, indicating dilated, compliant arterial vessels

nervous system

abnormal channel response ( J:281903 )

• whole-cell patch-clamp recordings show an approximate 5-fold higher basal potassium conductance in acutely isolated smooth muscle cells

• the effect of pinacidil, the K(ATP) channel opener, is blunted in vascular smooth muscle cells (does not provoke increase in conductance) and subsequent application of the K(ATP) channel inhibitor, glibenclamide, is less effective

growth/size/body

enlarged heart ( J:281903 )

• cardiomegaly results from cellular hypertrophy

increased heart weight ( J:281903 )

• 1.7-fold increase in heart weight

cardiac hypertrophy ( J:281903 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hypertrichotic osteochondrodysplasia Cantu type		DOID:0060569	OMIM:239850	J:281903

Genotype
MGI:6389026

cx3

• Allelic Composition: Abcc9^em1Nich/Abcc9⁺; Kcnj8^em1Nich/Kcnj8⁺
• Genetic Background: involves: C57BL/6J * CBA/J

mortality/aging

premature death ( J:281903 )

• mortality is increased compared to single homozygotes, with death shortly after weaning