Phenotypes Associated with This Genotype

Genotype
MGI:5659847

• Allelic Composition: Mto1^{Gt(G019A03)Wrst}/Mto1^{Gt(G019A03)Wrst}
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

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

behavior/neurological

abnormal behavioral response to anesthetic ( J:223246 )

• marked arrhythmias occur especially during induction and reversal of anesthesia

decreased anxiety-related response ( J:223246 )

• 8 week old mice exhibit reduced anxiety-related behavior in the modified Hole Board test, showing increased percentage of time spent on the board in the anxiogenic center of the test area and reduced percentage of time spent at the partition and in group contact with the cage mates

abnormal response to novel object ( J:223246 )

• 8 week old mice show increased object exploration in the modified Hole Board test

decreased startle reflex ( J:223246 )

• acoustic startle response shows an altered curve, with 9 week old mice showing lower response at maximum dB

abnormal motor coordination/balance ( J:223246 )

♀ • lighter weight females show a trend to improved performance on an accelerating rotarod at 10 weeks of age but not in aged mice

impaired coordination ( J:223246 )

♂ • males show impaired performance in advancing trials of the accelerating rotarod at 10 weeks of age but not in aged mice

increased grip strength ( J:223246 )

• grip strength measurements show a tendency towards more strength in mutants at 10 weeks of age but not in aged mice (16-20 months)

increased locomotor activity ( J:223246 )

• 8 week old mice exhibit increased horizontal locomotor activity in the modified Hole Board test, showing increased total distance traveled, mean velocity, and object exploration

cardiovascular system

decreased myocardial fiber mitochondrial DNA content ( J:223246 )

• in hearts

myocardial fiber degeneration ( J:223246 )

• 10 month old mice show focal signs of myofiber degeneration (atrophy and vacuolization) and fibrosis

cardiac muscle necrosis ( J:223246 )

• focal necrosis in cardiac muscle cells with intracristal swelling in mitochondria and dilated sarcoplasmic reticulum in young adult mice

increased heart weight ( J:223246 )

• heart weight at 22 weeks of age is increased related to body weight and is seen as a trend at 10 months of age

dilated heart ( J:223246 )

• slightly dilated hearts with increased diastolic and systolic internal left ventricular diameters

• however, fractional shortening is normal indicating that left ventricular function is preserved and posterior wall and septum thickness are normal

decreased heart rate ( J:223246 )

• heart rate is consistently reduced at different ages and conditions; in awake mice at 4 and 10 months, and in anaesthetized mice at 4 and 15 months

irregular heartbeat ( J:223246 )

• high incidence of arrhythmic events, with 16 of 19 mice showing arrhythmias, mainly atrioventricular blocks, but also premature ventricular beats or a higher degree of sinoatrial node blocks

• marked arrhythmias occur especially during induction and reversal of anesthesia

ventricular premature beat ( J:223246 )

• mice sometimes show premature ventricular beats

atrioventricular block ( J:223246 )

• mice mainly show atrioventricular blocks

decreased QRS amplitude ( J:223246 )

prolonged QRS complex duration ( J:223246 )

prolonged QT interval ( J:223246 )

• QT interval is slightly, but significantly increased

sinoatrial block ( J:223246 )

• mice sometimes show a higher degree of sinoatrial blocks

cardiomyopathy ( J:223246 )

cellular

decreased myocardial fiber mitochondrial DNA content ( J:223246 )

• in hearts

abnormal mitochondrial inner membrane morphology ( J:223246 )

• cardiac muscle cells of young mice exhibit mitochondria with intracristal swelling

abnormal mitochondrial physiology ( J:223246 )

• maximal respiration rate of isolated heart mitochondria normalized to total protein is reduced in mutants

• lower amounts of complex I protein is seen in heart mitochondria and a tendency towards reduced complex I activity

growth/size/body

increased heart weight ( J:223246 )

• heart weight at 22 weeks of age is increased related to body weight and is seen as a trend at 10 months of age

decreased body weight ( J:223246 )

• body weight at 10 weeks of age is reduced

homeostasis/metabolism

increased susceptibility to xenobiotic induced morbidity/mortality ( J:223246 )

• mice exhibit increased lethality compared to controls after treatment with the herbicide paraquat

increased physiological sensitivity to xenobiotic ( J:223246 )

• mice exhibit increased sensitivity to the herbicide paraquat, showing increased lethality and decreased locomotor activity

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:223246 )

• mice exhibit increased lethality compared to controls after treatment with the herbicide paraquat

muscle

decreased myocardial fiber mitochondrial DNA content ( J:223246 )

• in hearts

myocardial fiber degeneration ( J:223246 )

• 10 month old mice show focal signs of myofiber degeneration (atrophy and vacuolization) and fibrosis

cardiac muscle necrosis ( J:223246 )

• focal necrosis in cardiac muscle cells with intracristal swelling in mitochondria and dilated sarcoplasmic reticulum in young adult mice

cardiomyopathy ( J:223246 )

dilated sarcoplasmic reticulum ( J:223246 )

• cardiac muscle cells of young mice exhibit dilated sarcoplasmic reticulum

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
combined oxidative phosphorylation deficiency		DOID:0060286	OMIM:PS609060	J:223246