Phenotypes associated with this allele

• Allele Symbol: Chchd10^em3Dpn
• Allele Name: endonuclease-mediated mutation 3, Derek P Narendra
• Allele ID: MGI:7579274
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Chchd10^em3Dpn/Chchd10^em3Dpn	C57BL/6J-Chchd10^em3Dpn	MGI:7579308
cx2	Chchd10^em3Dpn/Chchd10^em3Dpn Oma1^tm1Otin/Oma1^tm1Otin	involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl	MGI:7579309
cx3	Chchd10^em3Dpn/Chchd10^em3Dpn Oma1^tm1Otin/Oma1^+	involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl	MGI:7579310

Genotype
MGI:7579308

hm1

• 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

Genotype
MGI:7579309

cx2

• Allelic Composition: Chchd10^em3Dpn/Chchd10^em3Dpn; Oma1^tm1Otin/Oma1^tm1Otin
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl

mortality/aging

neonatal lethality, incomplete penetrance ( J:344465 )

• neonatal lethality with few mice surviving to weaning

postnatal lethality, incomplete penetrance ( J:344465 )

• most pups die between P5 and P8, with the few survivors dying by 15 weeks of age

growth/size/body

enlarged heart ( J:344465 )

• mice that survive to 15 weeks of age have enlarged hearts

decreased body size ( J:344465 )

• mice that survive to 15 weeks of age exhibit decreased body size

decreased body weight ( J:344465 )

• body weight is lower at P5 but not at P1

cardiovascular system

enlarged heart ( J:344465 )

• mice that survive to 15 weeks of age have enlarged hearts

cellular

abnormal mitochondrial crista morphology ( J:344465 )

• heart mitochondria exhibit inclusions

abnormal mitochondrial shape ( J:344465 )

• surviving mice exhibit heart mitochondria that are longer but tend to have decreased caliber and thus smaller in volume

dilated mitochondrion ( J:344465 )

• megamitochondria, massively swollen mitochondria with lighter matrix density, are seen in hearts of 14-week-old mice

Genotype
MGI:7579310

cx3

• Allelic Composition: Chchd10^em3Dpn/Chchd10^em3Dpn; Oma1^tm1Otin/Oma1⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl

muscle

abnormal muscle fiber mitochondrial morphology ( J:344465 )

• hearts show mitochondrial fragmentation, megamitochondria, and inclusions due to reshaping of the inner membrane

cellular

abnormal mitochondrial morphology ( J:344465 )

• mice exhibit smaller heart mitochondria, reflecting mitochondrial fragmentation

abnormal mitochondrial crista morphology ( J:344465 )

• heart mitochondria exhibit inclusions due to reshaping of the inner membrane

abnormal muscle fiber mitochondrial morphology ( J:344465 )

• hearts show mitochondrial fragmentation, megamitochondria, and inclusions due to reshaping of the inner membrane

dilated mitochondrion ( J:344465 )

• megamitochondria, massively swollen mitochondria with lighter matrix density, are seen in hearts of 14-week-old mice