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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tg(Plp1-cre/ERT)3Pop
transgene insertion 3, Brian Popko
MGI:2450391
Summary 8 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Afg3l2tm1Arte/Afg3l2tm1Arte
Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+
Tg(Plp1-cre/ERT)3Pop/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J MGI:5817781
cn2
Afg3l1tm1.1Arte/Afg3l1tm1.1Arte
Afg3l2tm1Arte/Afg3l2tm1Arte
Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+
Tg(Plp1-cre/ERT)3Pop/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * C57BL/6N MGI:5817784
cn3
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Tg(Plp1-cre/ERT)3Pop/0
involves: 129S/SvEv * C57BL/6 * DBA/2 MGI:5796111
cn4
Cemiptm1.1Tac/Cemiptm1.1Tac
Tg(Plp1-cre/ERT)3Pop/0
involves: C57BL/6 * C57BL/6NTac * DBA/2 MGI:6117717
cn5
Nfasctm1Bhat/Nfasctm1Bhat
Tg(Plp1-cre/ERT)3Pop/?
involves: C57BL/6 * DBA/2 MGI:3836432
cn6
Afg3l2tm1Arte/Afg3l2tm1Arte
Tg(Plp1-cre/ERT)3Pop/0
involves: C57BL/6J MGI:5817780
cn7
Afg3l1tm1.1Arte/Afg3l1tm1.1Arte
Afg3l2tm1Arte/Afg3l2tm1Arte
Tg(Plp1-cre/ERT)3Pop/0
involves: C57BL/6J * C57BL/6N MGI:5817783
tg8
Tg(Plp1-cre/ERT)3Pop/0 involves: C57BL/6 * DBA/2 MGI:3696409


Genotype
MGI:5817781
cn1
Allelic
Composition
Afg3l2tm1Arte/Afg3l2tm1Arte
Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+
Tg(Plp1-cre/ERT)3Pop/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Afg3l2tm1Arte mutation (0 available); any Afg3l2 mutation (3 available)
Gt(ROSA)26Sortm1Lrsn mutation (0 available); any Gt(ROSA)26Sor mutation (504 available)
Tg(Plp1-cre/ERT)3Pop mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• at 8 weeks of age, oligodendrocytes in the corpus callosum of tamoxifen-treated mice exhibit fragmented mitochondria, unlike in control mice
• at 8 weeks of age, oligodendrocytes in the corpus callosum of tamoxifen-treated mice exhibit swollen mitochondria, unlike in control mice




Genotype
MGI:5817784
cn2
Allelic
Composition
Afg3l1tm1.1Arte/Afg3l1tm1.1Arte
Afg3l2tm1Arte/Afg3l2tm1Arte
Gt(ROSA)26Sortm1Lrsn/Gt(ROSA)26Sor+
Tg(Plp1-cre/ERT)3Pop/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * C57BL/6N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Afg3l1tm1.1Arte mutation (0 available); any Afg3l1 mutation (29 available)
Afg3l2tm1Arte mutation (0 available); any Afg3l2 mutation (3 available)
Gt(ROSA)26Sortm1Lrsn mutation (0 available); any Gt(ROSA)26Sor mutation (504 available)
Tg(Plp1-cre/ERT)3Pop mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• 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
• 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
• 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
• at 10 weeks of age, tamoxifen-treated mice show a reduction of mt-YFP signal within the sciatic nerve
• 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
• at 28 weeks of age, non-myelinated large caliber axons and multivesicular disintegration of adaxonal myelin lamellae are observed in the sciatic nerve

cellular
• at 6 weeks of age, oligodendrocytes of tamoxifen-treated mice exhibit swollen mitochondria
• 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

embryo
• 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

integument
• at 28 weeks of age, tamoxifen-treated mice show reduced fat deposited in the dermis
• however, general skin structure is normal

pigmentation
• at 28 weeks of age, c-KIT+ melanocytes are significantly reduced in dorsal skin




Genotype
MGI:5796111
cn3
Allelic
Composition
Gt(ROSA)26Sortm1(DTA)Jpmb/Gt(ROSA)26Sor+
Tg(Plp1-cre/ERT)3Pop/0
Genetic
Background
involves: 129S/SvEv * C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(DTA)Jpmb mutation (1 available); any Gt(ROSA)26Sor mutation (504 available)
Tg(Plp1-cre/ERT)3Pop mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• about 50% of mice die 52 weeks after tamoxifen injection

nervous system
• mice exhibit seizures starting around 40 weeks after tamoxifen injection
• focal lesions in tamoxifen treated mice are sites of active inflammation, frequently infiltrated by T cells, and contain a high density of microglia or macrophages
• mice show increased CD3+ T cells in the CNS as early as 7 weeks after tamoxifen injection, increased numbers of CD4+ T cells in the CNS at 10 and 40 weeks after tamoxifen injection, and increased numbers of MHCII+B7+ (CD80+CD86+) dendritic cells at 40 weeks after tamoxifen injection
• all recovered tamoxifen-treated mice develop secondary, late-onset neurological symptoms and demyelinating disease starting around 40 weeks after injection
• mice injected with MOG(35-55)-coupled polylactic-co-glycolic acid nanoparticles 32 weeks after tamoxifen injection show inhibition of disease progression
• mice exhibit rare focal lesions in the brainstem, cerebellum, and spinal cord at 40 weeks after tamoxifen injection
• at 1 year after tamoxifen injection, focal lesions in these regions are no longer seen
• white matter lesions in tamoxifen injected mice show presence of macrophages containing myelin debris and unmyelinated axons, indicating ongoing demyelination
• tamoxifen treated mice exhibit loss of oligodendrocytes, peaking 5 weeks after injection and recovering by 10 weeks
• brainstem shows an approximate 50% decrease in oligodendrocytes at 1 year after tamoxifen treatment
• however, substantial oligodendrocyte loss in other CNS areas is not seen at 1 year after tamoxifen treatment
• thinner myelin in both tamoxifen treated and untreated mice (due to leakiness of the cre-expressing transgene)
• axonal loss in the ventrolateral white matter of the cervical spinal cord (40%) and the optic nerve (55%) at 1 year after tamoxifen treatment
• tamoxifen treated mice exhibit widespread CNS demyelination, peaking 5 weeks after injection and recovering by 10 weeks
• mice exhibit widespread myelin loss at 1 year after tamoxifen injection
• mice not treated with tamoxifen show some myelin loss in most CNS areas at 52 weeks of age, indicating leakiness of the cre-expressing transgene
• untreated mice exhibit about 30% fewer unmyelinated axons in the corpus callosum compared to tamoxifen treated mice

behavior/neurological
• mice show impaired motor skills starting around 40 weeks after tamoxifen injection
• tamoxifen treated mice exhibit severe ataxia starting around 40 weeks after injection
• mice exhibit seizures starting around 40 weeks after tamoxifen injection

growth/size/body
• mice show weight loss starting around 40 weeks after tamoxifen injection

hematopoietic system
• activated CD4+ T cells are present in the CNS at 10 weeks after tamoxifen injection and both activated CD4+ T cells and antigen-presenting dendritic cells are present in the CNS 40 week after tamoxifen injection

immune system
• activated CD4+ T cells are present in the CNS at 10 weeks after tamoxifen injection and both activated CD4+ T cells and antigen-presenting dendritic cells are present in the CNS 40 week after tamoxifen injection
• total numbers of CD4+ T cells, CD8+ T cells, B cells, monocytes, and dendritic cells in the CNS-draining cervical lymph nodes of tamoxifen treated mice is higher than in controls
• at 40 weeks after tamoxifen injection, autoreactive T cells capable of proliferating in response to stimulation with recombinant MOG protein are seen in the spleen and cervical lymph nodes indicating an adaptive autoimmune response against myelin
• focal lesions in tamoxifen treated mice are sites of active inflammation, frequently infiltrated by T cells, and contain a high density of microglia or macrophages
• mice show increased CD3+ T cells in the CNS as early as 7 weeks after tamoxifen injection, increased numbers of CD4+ T cells in the CNS at 10 and 40 weeks after tamoxifen injection, and increased numbers of MHCII+B7+ (CD80+CD86+) dendritic cells at 40 weeks after tamoxifen injection

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
multiple sclerosis DOID:2377 OMIM:126200
OMIM:612594
OMIM:612595
OMIM:612596
OMIM:614810
J:234435




Genotype
MGI:6117717
cn4
Allelic
Composition
Cemiptm1.1Tac/Cemiptm1.1Tac
Tg(Plp1-cre/ERT)3Pop/0
Genetic
Background
involves: C57BL/6 * C57BL/6NTac * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cemiptm1.1Tac mutation (0 available); any Cemip mutation (37 available)
Tg(Plp1-cre/ERT)3Pop mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• tamoxifen-treated myelinated Schwann cells in culture exhibit reduced dedifferentiation compared with wild-type cells




Genotype
MGI:3836432
cn5
Allelic
Composition
Nfasctm1Bhat/Nfasctm1Bhat
Tg(Plp1-cre/ERT)3Pop/?
Genetic
Background
involves: C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nfasctm1Bhat mutation (0 available); any Nfasc mutation (8 available)
Tg(Plp1-cre/ERT)3Pop mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• after 20 days of tamoxifen treatment
• septal morphology of axons becomes progressively disorganized
• axolemma becomes detached from myelin loops
• moderate reduction of tibial/plantar conduction velocity in mice injected at days 23-33 with tamoxifen measured around 86 days of age




Genotype
MGI:5817780
cn6
Allelic
Composition
Afg3l2tm1Arte/Afg3l2tm1Arte
Tg(Plp1-cre/ERT)3Pop/0
Genetic
Background
involves: C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Afg3l2tm1Arte mutation (0 available); any Afg3l2 mutation (3 available)
Tg(Plp1-cre/ERT)3Pop mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• 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

nervous system
• 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
• at 56 weeks of age, a few axons in the spinal cord white matter exhibit thin myelin
• at 90 weeks of age, tamoxifen-treated mice show thickened myelin in the antero-lateral funiculi spinal cord white matter
• 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
• 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
• 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

cellular
• by 86 weeks of age, oligodendrocytes in the spinal cord white matter exhibit disrupted mitochondrial cristae
• by 86 weeks of age, oligodendrocytes in the spinal cord white matter contain enlarged mitochondria

growth/size/body
N
• tamoxifen-treated mice show no significant weight loss up 90 weeks of age




Genotype
MGI:5817783
cn7
Allelic
Composition
Afg3l1tm1.1Arte/Afg3l1tm1.1Arte
Afg3l2tm1Arte/Afg3l2tm1Arte
Tg(Plp1-cre/ERT)3Pop/0
Genetic
Background
involves: C57BL/6J * C57BL/6N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Afg3l1tm1.1Arte mutation (0 available); any Afg3l1 mutation (29 available)
Afg3l2tm1Arte mutation (0 available); any Afg3l2 mutation (3 available)
Tg(Plp1-cre/ERT)3Pop mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• at 13 and 28 weeks of age, tamoxifen-treated mice exhibit significantly decreased fat mass relative to single Afg3l1tm1.1Arte homozygous (control) mice
• 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

behavior/neurological
• 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

nervous system
• demyelination is associated with microglia activation
• tamoxifen-treated mice exhibit activated microglia in the corpus callosum at 28 weeks of age
• tamoxifen-treated mice show marked loss of white matter in the corpus callosum, internal capsule, and cerebellum at 28 weeks of age
• 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
• 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
• 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
• 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

pigmentation
• 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

adipose tissue
• at 13 and 28 weeks of age, tamoxifen-treated mice exhibit significantly decreased fat mass relative to single Afg3l1tm1.1Arte homozygous (control) mice

hematopoietic system
• demyelination is associated with microglia activation
• tamoxifen-treated mice exhibit activated microglia in the corpus callosum at 28 weeks of age

immune system
• demyelination is associated with microglia activation
• tamoxifen-treated mice exhibit activated microglia in the corpus callosum at 28 weeks of age

integument
• 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




Genotype
MGI:3696409
tg8
Allelic
Composition
Tg(Plp1-cre/ERT)3Pop/0
Genetic
Background
involves: C57BL/6 * DBA/2
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Plp1-cre/ERT)3Pop mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype
• mice ae fertile and appear normal; expression of cre is primarily restricted to myelinating oligodendrocytes of the CNS





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last database update
11/26/2019
MGI 6.14
The Jackson Laboratory