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Phenotypes Associated with This Genotype
Genotype
MGI:3808758
Allelic
Composition
Tk2tm1Mihi/Tk2tm1Mihi
Genetic
Background
involves: 129S6/SvEv * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tk2tm1Mihi mutation (0 available); any Tk2 mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging

behavior/neurological
• after P10, mice exhibit coarse tremors
• after P10, mice develop progressive weakness that leads to death
• after P10
• after P10, mice exhibit a severely impaired gait

nervous system
• mutants develop severe and progressive encephalomyelopathy
• dTTP levels are decreased in the brain of mutants by P8 and even further decreased by P13
• mitochondrial DNA depletion in the brain
• 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 vacuoles are present in spinal cord neurons

cellular
• 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)
• 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

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

cardiovascular system
• dTTP levels are decreased in the heart at P13
• mitochondrial DNA depletion in the heart

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


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
03/19/2019
MGI 6.13
The Jackson Laboratory