Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Afg3l2tm1Arte mutation
(0 available);
any
Afg3l2 mutation
(67 available)
Tg(Pcp2-cre)2Mpin mutation
(1 available)
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Purkinje cell degeneration in Afg3l2tm1Arte/Afg3l2tm1Arte Tg(Pcp2-cre)2Mpin/0 mice
nervous system
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• at 4 weeks, Purkinje cells have swollen mitochondria with disrupted cristae unlike control cells
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• impaired in Purkinje cells
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• disappearance of almost all neurons at 12 weeks
• however, normal numbers at 4 weeks
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• postnatal and progressive
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• loss observed at 6 weeks and progresses over time
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behavior/neurological
cellular
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• at 4 weeks, Purkinje cells have swollen mitochondria with disrupted cristae unlike control cells
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immune system
hematopoietic system
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Afg3l2tm1Arte mutation
(0 available);
any
Afg3l2 mutation
(67 available)
Gt(ROSA)26Sortm1Lrsn mutation
(1 available);
any
Gt(ROSA)26Sor mutation
(944 available)
Tg(Pcp2-cre)2Mpin mutation
(1 available)
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Abnormal mitochondrial network in Afg3l2tm1Arte/Afg3l2tm1Arte Tg(Pcp2-cre)2Mpin/0 Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+ mice
cellular
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• at 4 weeks, Purkinje cells exhibit fragmentation of mitochondria unlike control cells
• at 6 weeks, mitochondrial fragmentation is very pronounced
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nervous system
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• at 4 weeks, Purkinje cells exhibit fragmentation of mitochondria unlike control cells
• at 6 weeks, mitochondrial fragmentation is very pronounced
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• Purkinje cell electrophysiological properties are normal at 4 to 5 weeks of age
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Afg3l2tm1Arte mutation
(0 available);
any
Afg3l2 mutation
(67 available)
Gt(ROSA)26Sortm1Lrsn mutation
(1 available);
any
Gt(ROSA)26Sor mutation
(944 available)
Tg(Plp1-cre/ERT)3Pop mutation
(2 available)
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cellular
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• at 8 weeks of age, oligodendrocytes in the corpus callosum of tamoxifen-treated mice exhibit fragmented mitochondria, unlike in control mice
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• at 8 weeks of age, oligodendrocytes in the corpus callosum of tamoxifen-treated mice exhibit swollen mitochondria, unlike in control mice
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Afg3l1tm1.1Arte mutation
(0 available);
any
Afg3l1 mutation
(35 available)
Afg3l2tm1Arte mutation
(0 available);
any
Afg3l2 mutation
(67 available)
Gt(ROSA)26Sortm1Lrsn mutation
(1 available);
any
Gt(ROSA)26Sor mutation
(944 available)
Tg(Plp1-cre/ERT)3Pop mutation
(2 available)
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nervous system
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• at 10 weeks of age, tamoxifen-treated mice show a strong reduction of mt-YFP+ melanoblasts in the outer root sheath of the hair follicle
• at 28 weeks of age, pigmented hair follicles and c-KIT+ melanoblasts are significantly reduced in dorsal skin, suggesting that premature hair greying is caused by progressive loss of melanoblasts that share a common developmental origin with Schwann cells
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• tamoxifen-treated mice show progressive and rapid loss of targeted (mt-YFP+) oligodendrocytes in the corpus callosum after 6 weeks of age, with only a few targeted cells remaining at 28 weeks
• at 10 weeks, the number of total APC+ cells is significantly decreased both in the corpus callosum and in the spinal cord
• at 10 weeks, the % of mt-YFP+ cells in the corpus callosum that are also APC+ is significantly reduced, while the % of APC- Olig2- targeted cells is significantly increased
• surprisingly, the number of mature oligodendrocytes and the size of APC+ cells is increased at 28 weeks of age; enlarged APC+ cells do not co-localize with mt-YFP+ cells but are in fact intensively positive for Olig2 staining
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• at 10 weeks of age, non-myelinating Schwann cells in the subcutaneous nerve plexus show a significant decrease of mt-YFP signal
• at 10 weeks of age, tamoxifen-treated mice show clear signs of Schwann cell pathology affecting preferentially small calibre unmyelinated fibers; several Remak bundles appear affected with individual unmyelinated axons touching each other and showing initial signs of axonal degeneration; inner tongue swellings are also observed in myelinated axons
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• at 10 weeks of age, tamoxifen-treated mice show a reduction of mt-YFP signal within the sciatic nerve
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• tamoxifen-treated mice show death of mature oligodendrocytes followed by compensatory repopulation by untargeted oligodendrocytes
• at 8 weeks of age, several oligodendrocytes undergo dark cell death, a caspase-independent form of death characterized by strong cytoplasmic condensation, chromatin clumping, ruffling of the cell membrane, but no blebbing of the nucleus or plasma membrane
• only a few TUNEL+ apoptotic cells are noted in the corpus callosum at 7 weeks of age
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• at 28 weeks of age, non-myelinated large caliber axons and multivesicular disintegration of adaxonal myelin lamellae are observed in the sciatic nerve
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cellular
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• at 6 weeks of age, oligodendrocytes of tamoxifen-treated mice exhibit swollen mitochondria
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• at 8 but not at 6 weeks of age, oligodendrocytes of tamoxifen-treated mice exhibit loss of COX1 staining, indicating impaired mitochondrial function
• cytochrome c is undetectable in several swollen mitochondria in oligodendrocytes at 8 weeks of age
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embryo
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• at 10 weeks of age, tamoxifen-treated mice show a strong reduction of mt-YFP+ melanoblasts in the outer root sheath of the hair follicle
• at 28 weeks of age, pigmented hair follicles and c-KIT+ melanoblasts are significantly reduced in dorsal skin, suggesting that premature hair greying is caused by progressive loss of melanoblasts that share a common developmental origin with Schwann cells
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integument
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• at 28 weeks of age, tamoxifen-treated mice show reduced fat deposited in the dermis
• however, general skin structure is normal
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pigmentation
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• at 28 weeks of age, c-KIT+ melanocytes are significantly reduced in dorsal skin
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Afg3l2tm1Arte mutation
(0 available);
any
Afg3l2 mutation
(67 available)
Tg(Plp1-cre/ERT)3Pop mutation
(2 available)
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behavior/neurological
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• at 90 weeks of age, tamoxifen-treated mice show a mild but significant impairment in motor performance on an accelerating rotarod test
• however, no abnormalities in cage behavior are observed
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nervous system
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• at 90 weeks of age, tamoxifen-treated mice show only a few bigger oligodendrocytes (APC+ cells) in the corpus callosum
• by 86 weeks of age, oligodendrocytes in the spinal cord white matter contain enlarged mitochondria with disrupted cristae
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• at 56 weeks of age, a few axons in the spinal cord white matter exhibit thin myelin
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• at 90 weeks of age, tamoxifen-treated mice show thickened myelin in the antero-lateral funiculi spinal cord white matter
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• at 56 weeks of age, a few axons in the spinal cord white matter exhibit thin myelin while others show adaxonal myelin detachment and vacuolization
• by 86 weeks, degenerating axons are surrounded by damaged myelin or contain accumulation of material
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• at 90 weeks of age, tamoxifen-treated mice show abnormal myelin profiles characterized by myelin thickening, infoldings and myelin whorls, indicative of axonal degeneration, in the spinal cord
• however, myelination and axonal integrity is largely normal at 56 weeks of age
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• at 56 weeks, and more prominently at 86 weeks of age, tamoxifen-treated mice exhibit myelin disruption and myelin detachment in the spinal cord white matter
• however, no obvious demyelination is detected up to 90 weeks of age
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cellular
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• by 86 weeks of age, oligodendrocytes in the spinal cord white matter exhibit disrupted mitochondrial cristae
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• by 86 weeks of age, oligodendrocytes in the spinal cord white matter contain enlarged mitochondria
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growth/size/body
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• tamoxifen-treated mice show no significant weight loss up 90 weeks of age
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Afg3l1tm1.1Arte mutation
(0 available);
any
Afg3l1 mutation
(35 available)
Afg3l2tm1Arte mutation
(0 available);
any
Afg3l2 mutation
(67 available)
Tg(Plp1-cre/ERT)3Pop mutation
(2 available)
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growth/size/body
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• at 13 and 28 weeks of age, tamoxifen-treated mice exhibit significantly decreased fat mass relative to single Afg3l1tm1.1Arte homozygous (control) mice
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• starting at 8 weeks of age, tamoxifen-treated mice show decreased body weight relative to control mice
• difference in body weight persists even after adding food pellets directly in the cage
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behavior/neurological
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• at 11-13 weeks of age, tamoxifen-treated mice spend less time on the rotating rod than control mice
• during a beam walking test, the number of foot slips is significantly higher at 13 weeks and dramatically increased at 28 weeks of age relative to that in control mice
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nervous system
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• demyelination is associated with microglia activation
• tamoxifen-treated mice exhibit activated microglia in the corpus callosum at 28 weeks of age
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• tamoxifen-treated mice show marked loss of white matter in the corpus callosum, internal capsule, and cerebellum at 28 weeks of age
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• demyelination is associated with astrocyte activation, as shown by upregulation of GFAP in spinal cord and brain lysates at 10 and 28 weeks of age
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• tamoxifen-treated mice show progressive demyelination in the spinal cord white matter, with some axons showing adaxonal myelin detachment at 13 weeks and marked signs of demyelination at 18 weeks of age
• the g ratio, expressing the ratio between the diameter of the inner axon and the total fiber diameter, is significantly increased at 28 weeks of age
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• tamoxifen-treated mice show signs of secondary axonal degeneration in the spinal cord, with accumulation of organelles and material in axons at 28 weeks of age
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• tamoxifen-treated mice show progressive demyelination in the lumbar spinal cord, resulting in demyelinated and degenerating axons as well as dark cells in the antero-lateral funiculus at 28 weeks of age
• Gallyas' silver staining of brain myelinated tracts showed prominent loss of white matter in the corpus callosum, internal capsule, and cerebellum at 28 weeks of age
• progressive loss of myelin is confirmed by western blot analysis of myelin proteins in spinal cord and brain lysates at 10 and 28 weeks of age
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pigmentation
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• tamoxifen-treated mice show premature and progressive hair greying starting ventrally close to the forelimbs at 10 weeks, resulting in a grey belly at 17 weeks, and finally extending to the dorsal skin at 28 weeks of age; no such phenotype is observed in control mice
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adipose tissue
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• at 13 and 28 weeks of age, tamoxifen-treated mice exhibit significantly decreased fat mass relative to single Afg3l1tm1.1Arte homozygous (control) mice
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hematopoietic system
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• demyelination is associated with microglia activation
• tamoxifen-treated mice exhibit activated microglia in the corpus callosum at 28 weeks of age
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immune system
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• demyelination is associated with microglia activation
• tamoxifen-treated mice exhibit activated microglia in the corpus callosum at 28 weeks of age
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integument
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• tamoxifen-treated mice show premature and progressive hair greying starting ventrally close to the forelimbs at 10 weeks, resulting in a grey belly at 17 weeks, and finally extending to the dorsal skin at 28 weeks of age; no such phenotype is observed in control mice
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Analysis Tools