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Phenotypes Associated with This Genotype
Genotype
MGI:5796111
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 (2 available); any Gt(ROSA)26Sor mutation (765 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:612594
OMIM:612595
OMIM:612596
J:234435


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
08/03/2022
MGI 6.21
The Jackson Laboratory