Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mfn2tm1Dcc mutation
(0 available);
any
Mfn2 mutation
(26 available)
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Defective giant cell layer of Mfn2tm1Dcc/Mfn2tm1Dcc placenta
mortality/aging
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• frequency of homozygous embryos normal up to E9.5
• 29% of homozygotes resorbed at E10.5
• 87% of homozygotes resorbed at E11.5
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embryo
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• embryos slightly smaller than littermates between E9.5 and E10.5 embryos slightly smaller than littermates between E9.5 and E10.5
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• reduced numbers of trophoblast giant cells
• form an incomplete layer only one cell layer thick in placentas from E8.5-E10.5
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cellular
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• spherical or oval shaped mitochondria
• with cristae and a double membrane
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• individual mitochondria functionally defective
• fewer mitochondrial fusion events observed
• mobility impaired secondary to abnormalities in shape
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growth/size/body
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• embryos slightly smaller than littermates between E9.5 and E10.5 embryos slightly smaller than littermates between E9.5 and E10.5
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Allelic
Composition |
Mfn2tm1Dcc/Mfn2tm3Dcc
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Genetic
Background |
involves: 129 * 129S4/SvJaeSor * Black Swiss |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mfn2tm1Dcc mutation
(0 available);
any
Mfn2 mutation
(26 available)
Mfn2tm3Dcc mutation
(2 available);
any
Mfn2 mutation
(26 available)
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cellular
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• fibroblast derived from mutant animals exhibit Cre-dependent mitochondrial fragmentation
• loss of mtDNA nucleoids from a significant fraction of mitochondria
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normal phenotype
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• shows no defect in balance and coordination
• no anatomical abnormality in cerebella
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nervous system
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• Purkinje cell death in 9 weeks-old mutant mice cerebella
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• Purkinje cell dendrite attenuation in 9 weeks-old mutant mice cerebella
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cellular
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• decreased cytochrome C oxidase activity and increased succinate dehydrogenase activity in Purkinje cells of 9-weeks-old mutant mice indicating the electron transport chain dysfunction in mitochondria
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mortality/aging
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• mutant pups are born at appropriate Mendelian ratio
• after birth, about one third of mutant mice die on postnatal day 1
• all remaining mutant mice die by P17
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behavior/neurological
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• mice surviving beyond P1 cannot easily regain posture when placed on their backs
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• mice surviving beyond P1 display uncoordinated limb movements, and move primarily by writhing on their abdomen
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growth/size/body
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• mice surviving beyond P1 are severely runted, likely due to feeding problems secondary to their movement disorder
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nervous system
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• severe defect in postnatal cerebellar growth
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mortality/aging
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• mutant pups are born at appropriate Mendelian ratio
• after birth, about one third of mutant mice die on postnatal day 1
• all remaining mutant mice die by P17
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behavior/neurological
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• mice surviving beyond P1 cannot easily regain posture when placed on their backs
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• mice surviving beyond P1 display uncoordinated limb movements, and move primarily by writhing on their abdomen
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growth/size/body
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• mice surviving beyond P1 are severely runted, likely due to feeding problems secondary to their movement disorder
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nervous system
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• mitochondria in mutant Purkinje cells in mixed cerebellar cultures tend to cluster together in the cell body and do not enter the dendritic tracts
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• markedly higher levels of apoptosis in mutant cerebella as early as p6 and continuing through the second postnatal week
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• widespread loss of Purkinje cell bodies py P15 resulting in reduction of the molecular layer
• Purkinje cell loss due to a degenerative process in mixed cerebellar cultures
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• reduced growth and deterioration of Purkinje cell dendrite during the second postnatal week
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• severe defect in postnatal cerebellar growth
• between P7 and P16, the mutant cerebellum reduces in size
• lobular organization and formation of the three cellular layers is relatively intact
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cellular
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• mitochondria in mutant Purkinje cells in mixed cerebellar cultures tend to cluster together in the cell body and do not enter the dendritic tracts
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• markedly higher levels of apoptosis in mutant cerebella as early as p6 and continuing through the second postnatal week
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mfn2tm1Dcc mutation
(0 available);
any
Mfn2 mutation
(26 available)
Mfn2tm3Dcc mutation
(2 available);
any
Mfn2 mutation
(26 available)
Tg(Pcp2-cre)2Mpin mutation
(1 available)
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behavior/neurological
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• a progressive decline in coordination and balance in rotarod test
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• at 2 months of age, they begin to exhibit a slightly shaky gait
• mutants are indistinguishable from wild-type littermates first 2 mo
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nervous system
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• ultrastructurally the mitochondria in mutant Purkinje cells shows dramatic defects in mitochondrial morphology, distribution, and cristae organization
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• obvious neuro-degeneration of cerebella over time
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• the dendrites and death of Purkinje cell bodies resulting in very few surviving Purkinje cells by 3 months
• essentially all Purkinje cells are gone at 6 months of age
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• Purkinje cell dendrite attenuation in 9 weeks-old mutant mice cerebella
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• by 3 months of age, the mutant cerebella are only 75% that of wild-type
• by 1 year of age, the overall cerebellar area of mutants has dropped to 50% of wild-type
• the greatest loss occurs in the molecular layer
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• by 7 weeks, mutant axons show extensive torpedoes, focal swellings typical of many neuropathies
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cellular
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• ultrastructurally the mitochondria in mutant Purkinje cells shows dramatic defects in mitochondrial morphology, distribution, and cristae organization
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• ecreased cytochrome C oxidase activity and increased succinate dehydrogenase activity in Purkinje cells of 9-weeks-old mutant mice indicating the electron transport chain dysfunction in mitochondria
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mfn2tm1Dcc mutation
(0 available);
any
Mfn2 mutation
(26 available)
Mfn2tm3Dcc mutation
(2 available);
any
Mfn2 mutation
(26 available)
Tg(EIIa-cre)C5379Lmgd mutation
(4 available)
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mortality/aging
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• embryos die during mid-gestation similar to Mfn2tm1Dcc homozygous embryos
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behavior/neurological
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• mice surviving beyond P1 cannot easily regain posture when placed on their backs
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• mice surviving beyond P1 display uncoordinated limb movements, and move primarily by writhing on their abdomen
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growth/size/body
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• mice surviving beyond P1 are severely runted, likely due to feeding problems secondary to their movement disorder
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nervous system
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• severe defect in postnatal cerebellar growth
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mortality/aging
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• after birth, about one third of mutant mice die on postnatal day 1
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• mutant mice that survive the neonatal period die by P17
• mutant pups are born at appropriate Mendelian ratio
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mortality/aging
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• after birth, about one third of mutant mice die on postnatal day 1
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• mutant pups are born at appropriate Mendelian ratio
• mutant mice that survive the neonatal period die by P17
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behavior/neurological
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• mice surviving beyond P1 cannot easily regain posture when placed on their backs
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• mice surviving beyond P1 display uncoordinated limb movements, and move primarily by writhing on their abdomen
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growth/size/body
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• mice surviving beyond P1 are severely runted, likely due to feeding problems secondary to their movement disorder
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mfn1tm1Dcc mutation
(0 available);
any
Mfn1 mutation
(44 available)
Mfn2tm1Dcc mutation
(0 available);
any
Mfn2 mutation
(26 available)
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mortality/aging
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• death occurs earlier than when either allele is singly homozygous
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Analysis Tools