Phenotypes Associated with This Genotype

Genotype
MGI:5796111

• Allelic Composition: Gt(ROSA)26Sor^tm1(DTA)Jpmb/Gt(ROSA)26Sor⁺; Tg(Plp1-cre/ERT)3Pop/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * DBA/2

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:234435 )

• about 50% of mice die 52 weeks after tamoxifen injection

nervous system

seizures ( J:234435 )

• mice exhibit seizures starting around 40 weeks after tamoxifen injection

CNS inflammation ( J:234435 )

• 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

abnormal nervous system morphology ( J:234435 )

• 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

abnormal brain white matter morphology ( J:234435 )

• white matter lesions in tamoxifen injected mice show presence of macrophages containing myelin debris and unmyelinated axons, indicating ongoing demyelination

decreased oligodendrocyte number ( J:234435 )

• 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

decreased myelin sheath thickness ( J:234435 )

• thinner myelin in both tamoxifen treated and untreated mice (due to leakiness of the cre-expressing transgene)

axon degeneration ( J:234435 )

• axonal loss in the ventrolateral white matter of the cervical spinal cord (40%) and the optic nerve (55%) at 1 year after tamoxifen treatment

demyelination ( J:234435 )

• 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

abnormal motor coordination/balance ( J:234435 )

• mice show impaired motor skills starting around 40 weeks after tamoxifen injection

ataxia ( J:234435 )

• tamoxifen treated mice exhibit severe ataxia starting around 40 weeks after injection

seizures ( J:234435 )

• mice exhibit seizures starting around 40 weeks after tamoxifen injection

growth/size/body

weight loss ( J:234435 )

• mice show weight loss starting around 40 weeks after tamoxifen injection

hematopoietic system

increased activated T cell number ( J:234435 )

• 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

increased activated T cell number ( J:234435 )

• 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

lymph node inflammation ( J:234435 )

• 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

autoimmune response ( J:234435 )

• 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

CNS inflammation ( J:234435 )

• 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