Phenotypes Associated with This Genotype

Genotype
MGI:7579308

• Allelic Composition: Chchd10^em3Dpn/Chchd10^em3Dpn
• Genetic Background: C57BL/6J-Chchd10^em3Dpn

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

mortality/aging

premature death ( J:344465 )

• mice die prematurely

growth/size/body

decreased body size ( J:344465 )

decreased body weight ( J:344465 )

• decrease in body weight which is already evident at weaning

• however, total food intake is normal and there is no difference in the percentage of lean and fat mass

behavior/neurological

impaired coordination ( J:344465 )

• mice exhibit worse rotarod performance when tested at 18 weeks

• mice take longer to descend a 50 cm pole

decreased grip strength ( J:344465 )

impaired exercise endurance ( J:344465 )

• mice exhibit increased treadmill-induced fatigue

muscle

decreased myocardial fiber mitochondrial DNA content ( J:344465 )

• mice exhibit multiple mtDNA deletions and decreased mtDNA copy numbers in the heart

abnormal tibialis anterior morphology ( J:344465 )

• tibialis muscle exhibit increased lipid droplets

decreased skeletal muscle fiber size ( J:344465 )

• muscle fiber size is smaller but no COX- fibers are seen

myopathy ( J:344465 )

• mice exhibit myopathy, with smaller leg muscles

cardiovascular system

abnormal heart morphology ( J:344465 )

• CHCHD10 protein aggregates are prominent in hearts; protein form punctate aggregates that are mostly within the mitochondrial boundary

decreased myocardial fiber mitochondrial DNA content ( J:344465 )

• mice exhibit multiple mtDNA deletions and decreased mtDNA copy numbers in the heart

abnormal heart echocardiography feature ( J:344465 )

• mice exhibit decreased heart function as measured by echocardiography

atrioventricular block ( J:344465 )

cellular

decreased myocardial fiber mitochondrial DNA content ( J:344465 )

• mice exhibit multiple mtDNA deletions and decreased mtDNA copy numbers in the heart

abnormal mitochondrial crista morphology ( J:344465 )

• heart and skeletal muscle show intracristal inclusions that are enclosed within mitochondria and are formed from the cristal membrane with which they are continuous; they represent dilations of cristae

• inward budding events of the cristal membrane into the intracristal space

• however, no signs of substantial oxidative damage or mitophagy are seen in hearts

abnormal mitochondrial physiology ( J:344465 )

• complex I and complex IV activities are diminished in heart and muscle

limbs/digits/tail

abnormal tibialis anterior morphology ( J:344465 )

• tibialis muscle exhibit increased lipid droplets

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:344465 )

N • the respiratory exchange ratio tends to be higher at night (indicating increased carbohydrate reliance) and lower during the day (indicating increased fatty acid reliance), although not significantly

N • mice show no difference in oxygen consumption, carbon dioxide production or energy expenditure when accounting for body weight

impaired exercise endurance ( J:344465 )

• mice exhibit increased treadmill-induced fatigue

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
isolated mitochondrial myopathy		DOID:0081357	OMIM:616209	J:344465