Phenotypes Associated with This Genotype

Genotype
MGI:2387325

• Allelic Composition: Aifm1^Hq/Aifm1^Hq
• Genetic Background: B6CBACa A^w-J/A-Aifm1^Hq/J

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:110278 )

♀ • significantly reduced survival at both 1 and 4 weeks after transverse aortic banding

premature death ( J:144096 )

♀ • about 30% of mice die during the first 6 months, with most deaths occurring between 15 and 30 days of age

growth/size/body

cardiac hypertrophy ( J:110278 )

♀ • hypertrophy due to transverse aorting banding is twice as great as is seen in controls

decreased birth weight ( J:144096 )

♀

decreased body size ( J:144096 )

♀

decreased body weight ( J:144096 )

♀ • body weight varies widely

behavior/neurological

abnormal seizure response to pharmacological agent ( J:98103 )

♀ • mice are protected against CA3 region damage at both 4 and 7 days after kainic acid induced stage 4 seizures although some cell damage is observed

abnormal motor capabilities/coordination/movement ( J:79052 )

♀

tremors ( J:79052 )

♀ • age of onset is approximately 5 months

♀ • a perceptible lateral tremor at rest by 9 months of age

ataxia ( J:79052 , J:144096 )

♀ • age of onset is approximately 5 months of age (J:79052)

♀ • mild (J:79052)

♀ • truncal ataxia by 9 months (J:79052)

♀ • ataxia is seen in most mice at 3 months of age and by 6 months of age, 90% of mice show severe ataxia while 8% have no signs of ataxia (J:144096)

impaired coordination ( J:144096 )

♀ • mice show impaired coordination on the rotarod from 4 months of age

abnormal gait ( J:79052 )

♀ • side by side unsteady gait at 5 months of age

♀ • marked lateral swaying when moving and at rest by 9 months of age

nervous system

abnormal seizure response to pharmacological agent ( J:98103 )

♀ • mice are protected against CA3 region damage at both 4 and 7 days after kainic acid induced stage 4 seizures although some cell damage is observed

decreased susceptibility to neuronal excitotoxicity ( J:98103 )

♀ • resistant to cell death induced by glutamate, NMDA, and kainic acid

abnormal cerebellar cortex morphology ( J:78983 )

♀

Purkinje cell degeneration ( J:78983 , J:79052 )

♀ • Purkinje cell loss occurs later than granule cell loss (J:78983)

♀ • cell loss apparently due to necrosis (J:78983)

♀ • many Purkinje cells are dead by 7 months of age (J:78983)

♀ • described as mild and patchy in the folia, but extensive in the floccular lobes in mice 5-8 months of age (J:79052)

abnormal cerebellar granule layer morphology ( J:78983 , J:79052 )

♀ • losses are preferentially from the caudal vermis and hemispheres (J:78983)

♀ • most caudal granule cells are lost by 12 months (J:78983)

♀ • no reduction in the folia but extensive loss in the floccular lobes in mice 5-8 months of age (J:79052)

abnormal cerebellar granule cell morphology ( J:78983 )

♀ • pyknotic granule cell nuclei at 4 months of age

♀ • apoptotic granule cells seen at 4 months of age

small cerebellum ( J:78983 )

♀ • cerebellum normal before 3 months

♀ • much smaller at 7 months

amacrine cell degeneration ( J:78983 )

♀ • cell loss is seen in the ganglion layer after about 3 months of age

retina ganglion cell degeneration ( J:78983 )

♀ • ganglion cell loss is seen after about 3 months of age

absent optic nerve ( J:144096 )

♀ • ocular hypoplasia, with absence of the optic nerve in 40% of mice at 1 month of age

vision/eye

amacrine cell degeneration ( J:78983 )

♀ • cell loss is seen in the ganglion layer after about 3 months of age

retina ganglion cell degeneration ( J:78983 )

♀ • ganglion cell loss is seen after about 3 months of age

absent optic nerve ( J:144096 )

♀ • ocular hypoplasia, with absence of the optic nerve in 40% of mice at 1 month of age

thin retina inner plexiform layer ( J:78983 )

♀ • thinning by 11 months

thin retina outer plexiform layer ( J:78983 )

♀ • thinning by 11 months

increased susceptibility to age-related retinal degeneration ( J:78983 )

♀ • onset of retinal degeneration is after 3 months of age

♀ • cell loss is seen in all layers of the retina by 11 months

abnormal eye electrophysiology ( J:78983 )

♀ • both rod and cone ERG are diminished by 4 months of age

♀ • ERG responses are completely abolished by 10 months of age

cellular

abnormal cell cycle ( J:78983 )

♀ • cerebellar granule cells and retina cells re-enter the cell cycle with greater frequency than in controls

♀ • number of cycling cells in the cerebellum and retina increase through 7 months and then declines

increased cellular sensitivity to hydrogen peroxide ( J:78983 )

♀ • granule cells of the cerebellum in culture show increased sensitivity to hydrogen peroxide

increased cardiomyocyte apoptosis ( J:110278 )

♀ • greatly increased levels of both apoptosis and necrosis in myocytes after transverse aortic banding

decreased susceptibility to neuronal excitotoxicity ( J:98103 )

♀ • resistant to cell death induced by glutamate, NMDA, and kainic acid

abnormal respiratory electron transport chain ( J:144096 )

♀ • respiratory chain complex I deficiency is detected at 1 month of age and is seen in the cerebellum, thalamus, cortical-enriched brain fractions, optic nerves, and retinas at 6 months of age, with activity about 50% of wild-type levels in the cerebellum

♀ • respiratory chain complex I activity is reduced by 20% in the spinal cord, by 10% in kidney, and by 30% in skeletal muscle and is normal in heart, liver, and testis

♀ • complex I deficiency is greatest by 1 month of age in the cerebellum and skeletal muscle, while it is modest or absent in the thalamus, cortex, and optic nerve at 1 month of age and reaches 50% by 6 months of age

oxidative stress ( J:78983 , J:110278 )

♀ • increased sensitivity of the cerebellum to oxidative stress (J:78983)

♀ • oxidative damage to mitochondria of the cerebellar granular layer and the ganglion layer of the retina (J:78983)

♀ • slightly increased as a result of transverse aortic banding (J:110278)

cardiovascular system

abnormal cardiovascular system morphology ( J:110278 )

♀

cardiac hypertrophy ( J:110278 )

♀ • hypertrophy due to transverse aorting banding is twice as great as is seen in controls

dilated heart left ventricle ( J:110278 )

♀ • increased left ventricular internal diameter relative to controls as a result of transverse aortic banding

abnormal cardiovascular system physiology ( J:110278 )

♀

decreased cardiac muscle contractility ( J:110278 )

♀ • deterioration of cardiac contractility as a result of transverse aortic banding

abnormal myocardial fiber physiology ( J:110278 )

♀ • cardiomyocytes more prone to die in response to exposure to hydrogen peroxide

abnormal response to cardiac infarction ( J:110278 )

♀ • increased sensitivity to ischemia/reperfusion injury

♀ • over 80% fail to survive 30minutes of left anterior descending artery occlusion followed by 2 to 24 hours of reperfusion

increased myocardial infarct size ( J:110278 )

♀ • experimental infarction size is increased by 50% over controls in 2 month old animals and by 78% in 6 month old animals

♀ • apoptosis in viable muscle cells is also increased

muscle

decreased cardiac muscle contractility ( J:110278 )

♀ • deterioration of cardiac contractility as a result of transverse aortic banding

increased cardiomyocyte apoptosis ( J:110278 )

♀ • greatly increased levels of both apoptosis and necrosis in myocytes after transverse aortic banding

homeostasis/metabolism

abnormal response to cardiac infarction ( J:110278 )

♀ • increased sensitivity to ischemia/reperfusion injury

♀ • over 80% fail to survive 30minutes of left anterior descending artery occlusion followed by 2 to 24 hours of reperfusion

increased myocardial infarct size ( J:110278 )

♀ • experimental infarction size is increased by 50% over controls in 2 month old animals and by 78% in 6 month old animals

♀ • apoptosis in viable muscle cells is also increased

decreased susceptibility to neuronal excitotoxicity ( J:98103 )

♀ • resistant to cell death induced by glutamate, NMDA, and kainic acid

increased superoxide dismutase level ( J:144096 )

♀ • mice exhibit moderately elevated superoxide dismutase activities at 6 months of age in skeletal muscle

increased catalase activity ( J:78983 , J:144096 )

♀ • catalase activity increased in the cerebellum at 1 and 3 months of age (J:78983)

♀ • mice exhibit moderately elevated catalase activities at 6 months of age in skeletal muscle (J:144096)

integument

alopecia ( J:144096 )

♀ • complete baldness in most mice initially, followed by some hair growth resulting in a patchy or near-normal coat

♀ • at 3 months of age, about 50% of mice are bald over more than 30% of their body and about 30% have near-normal fur, and 10% of mice have near-normal fur at 6 months of age

sparse hair ( J:79052 )

♀ • described as nearly bald

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mitochondrial complex I deficiency		DOID:0060536		J:144096