Phenotypes Associated with This Genotype

Genotype
MGI:3808758

• Allelic Composition: Tk2^tm1Mihi/Tk2^tm1Mihi
• Genetic Background: involves: 129S6/SvEv * C57BL/6J

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

mortality/aging

postnatal lethality, complete penetrance ( J:139195 )

• mice die by P14

behavior/neurological

tremors ( J:139195 )

• after P10, mice exhibit coarse tremors

weakness ( J:139195 )

• after P10, mice develop progressive weakness that leads to death

abnormal gait ( J:139195 )

• after P10, mice exhibit a severely impaired gait

decreased locomotor activity ( J:139195 )

• after P10

nervous system

abnormal nervous system morphology ( J:139195 )

• mutants develop severe and progressive encephalomyelopathy

abnormal brain morphology ( J:166725 )

• dTTP levels are decreased in the brain of mutants by P8 and even further decreased by P13

• mitochondrial DNA depletion in the brain

abnormal astrocyte morphology ( J:139195 )

• unlike in wild-type mice, astrocytes are present in the brain and spinal cord with enlarged cell bodies and processes indicating activated glial cells

abnormal spinal cord interneuron morphology ( J:139195 )

• abnormal vacuoles are present in spinal cord neurons

cellular

decreased mitochondrial DNA content ( J:139195 , J:166725 )

• at P12, mitochondrial DNA content in the brain, heart, spinal cord, muscle and kidney is decreased to 12.5%, 20%, 15%, 32% and 60%, respectively, of levels in wild-type mice (J:139195)

• mitochondrial DNA depletion in the brain and heart (J:166725)

decreased muscle fiber mitochondrial DNA content ( J:166725 )

decreased myocardial fiber mitochondrial DNA content ( J:166725 )

abnormal mitochondrial ATP synthesis coupled electron transport ( J:139195 )

• brain showed decreased activities of respiratory chain enzymes with mtDNA-encoded subunits normalized to activity of citrate synthase (CS), a marker of mitochondrial mass; complex I activity was 40% and complex IV activity was 55% of wild-type mice

• reductions in ATP and ATP/ADP ratio in brain of mutant mice

• significant reductions in mutant brain of subunit 6 of complex I (73% of levels in controls) and subunit I of cytochrome c oxidase (67%) corresponded to the diminished activities of respiratory chain complexes I and IV

growth/size/body

postnatal growth retardation ( J:139195 )

• after P10

muscle

muscle phenotype ( J:139195 )

N • muscles contain normal fibers and exhibit normal proliferation of mitochondria

decreased muscle fiber mitochondrial DNA content ( J:166725 )

decreased myocardial fiber mitochondrial DNA content ( J:166725 )

cardiovascular system

abnormal heart morphology ( J:166725 )

• dTTP levels are decreased in the heart at P13

• mitochondrial DNA depletion in the heart

decreased myocardial fiber mitochondrial DNA content ( J:166725 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mitochondrial DNA depletion syndrome 2		DOID:0080120	OMIM:609560	J:139195 , J:166725