Phenotypes associated with this allele
nervous system
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• YFP+ neurons exhibit one or more grossly enlarged, rounded mitochondria in the perinuclear region of the soma and in proximal segment of dendrites with some cells containing fragmented mitochondria and small, spherical mitochondrial clustered around the nucleus
• YFP+ neurons exhibit a progressive reduction in distal axonal mitochondrial numbers compared with control cells
• however, mitochondria in the distal dopamine axons are morphologically spared
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• neurons exhibit less intense staining with a retrograde tracer (fluorogold) suggesting impaired retrograde transport and/or uptake of the tracer compared with control cells
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1Lrsn mutation
(1 available);
any
Gt(ROSA)26Sor mutation
(944 available)
Mfn2tm1.1Arte mutation
(0 available);
any
Mfn2 mutation
(26 available)
Slc6a3tm1(cre)Lrsn mutation
(1 available);
any
Slc6a3 mutation
(66 available)
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nervous system
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• profound reduction in the number of labeled mitochondria in the dorsal striatum
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• mitochondria are spherical and enlarged with disorganized cristae
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cellular
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• mitochondria in dopaminergic neurons are spherical and enlarged with disorganized cristae
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• profound reduction in the number of labeled mitochondria in the dorsal striatum
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• mitochondria in dopaminergic neurons are spherical and enlarged with disorganized cristae
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Mitochondria abnormalities in Tfamtm1Lrsn/Tfamtm1Lrsn Slc6a3tm1(cre)Lrsn/Slc6a3+ Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+ neurons
nervous system
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• YFP+ neurons exhibit one or more grossly enlarged, rounded mitochondria in the perinuclear region of the soma and in proximal segment of dendrites with some cells containing fragmented mitochondria and small, spherical mitochondrial clustered around the nucleus
• YFP+ neurons exhibit a progressive reduction in distal axonal mitochondrial numbers compared with control cells
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cellular
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• smaller mitochondrial and the largest aggregates in a rare number of neurons exhibit reduced import competence compared with mitochondria in control cells
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behavior/neurological
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• impaired from 20 weeks of age
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growth/size/body
muscle
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• rigidity from 20 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(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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Analysis Tools