Analysis Tools|
Allele Symbol Allele Name Allele ID |
Tg(Tcra2D2,Tcrb2D2)1Kuch transgene insertion 1, Vijay Kuchroo MGI:3700794 |
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| Summary |
15 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• between 15% and 20% of mice develop spontaneous EAE
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| multiple sclerosis | DOID:2377 |
OMIM:612594 OMIM:612595 OMIM:612596 |
J:151335 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• disease started between 7 and 10 weeks of age, with classical paralytic EAE signs
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• in a minority of cases, with a spastic component
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• inflammatory infiltrates in the trigeminal ganglia, spinal ganglia, spinal roots despite the absence of MOG within these tissues
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• inflammatory infiltrates in the peripheral nervous system despite the absence of MOG within these tissues
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• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in optic nerve
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• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in the spinal cord
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• within the spinal cord and optic nerve
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• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in optic nerve
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• 15% of the mice develop spontaneous EAE
|
|
• inflammatory infiltrates in the trigeminal ganglia, spinal ganglia, spinal roots despite the absence of MOG within these tissues
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| multiple sclerosis | DOID:2377 |
OMIM:612594 OMIM:612595 OMIM:612596 |
J:151335 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• disease started between 7 and 10 weeks of age, with classical paralytic EAE signs
|
|
• fifty percent spontaneously develop opticospinal myelitis
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• inflammatory infiltrates in the trigeminal ganglia, spinal ganglia, spinal roots despite the absence of MOG within these tissues
|
|
• in a minority of cases, with a spastic component
|
|
• inflammatory infiltrates in the trigeminal ganglia, spinal ganglia, spinal roots despite the absence of MOG within these tissues
|
|
• inflammatory infiltrates in the peripheral nervous system despite the absence of MOG within these tissues
|
|
• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in optic nerve
|
|
• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in the spinal cord
|
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• within the spinal cord and optic nerve
|
|
• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in optic nerve
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| multiple sclerosis | DOID:2377 |
OMIM:612594 OMIM:612595 OMIM:612596 |
J:151335 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in conjunction with anti-CTLA-4 antibody treatment, mice exhibit reduced paralysis induced by experimental autoimmune encephalomyelitis (EAE) compared to wild type mice
• however, adoptive transfer of Gt(ROSA)26Sortm2Awai Cd19tm1(cre)Cgn double heterozygous B cells increases paralysis induced by EAE despite treatment with anti-CTLA-4 antibodies compared to wild-type mice receiving Gt(ROSA)26Sortm2Awai Cd19tm1(cre)Cgn double heterozygous B cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit accelerated onset and succumb to complete hindlimb paralysis faster than control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• spontaneous EAE develops in two out of six mice
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| multiple sclerosis | DOID:2377 |
OMIM:612594 OMIM:612595 OMIM:612596 |
J:151335 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• disease started between 7 and 10 weeks of age, with classical paralytic EAE signs
|
|
• between 15% and 20% of mice develop spontaneous EAE
|
|
• inflammatory infiltrates in the trigeminal ganglia, spinal ganglia, spinal roots despite the absence of MOG within these tissues
|
|
• in a minority of cases, with a spastic component
|
|
• inflammatory infiltrates in the trigeminal ganglia, spinal ganglia, spinal roots despite the absence of MOG within these tissues
|
|
• inflammatory infiltrates in the peripheral nervous system despite the absence of MOG within these tissues
|
|
• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in optic nerve
|
|
• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in the spinal cord
|
|
• within the spinal cord and optic nerve
|
|
• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in optic nerve
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| multiple sclerosis | DOID:2377 |
OMIM:612594 OMIM:612595 OMIM:612596 |
J:151335 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit accelerated onset compared with control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• CD4 T cells are highly susceptible to dose-dependent suppression by CD8 T regulatory cells in vitro
• this suppression is dependent on Fas ligand being expressed by the CD8 T regulatory cell
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• transfer of CD4 T cells into Rag2-/- Prf1-/- hosts initiates a progressive and lethal form of EAE that results in death from fulminant disease within 14?16 days after transfer
• co-transfer of CD8 T regulatory cells with mutant CD4 T cells prevents disease where as co-transfer of CD8 T regulatory cells with transgenic CD4 T cells not carrying the H2-T23 mutation fails to prevent disease
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• CD4 T cells are highly susceptible to dose-dependent suppression by CD8 T regulatory cells in vitro
• this suppression is dependent on Fas ligand being expressed by the CD8 T regulatory cell
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• CD4 T cells are fully resistant to suppression by CD8 T regulatory cells in vitro as measured by proliferation and IL-2 secretion
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• CD4 T cells are fully resistant to suppression by CD8 T regulatory cells in vitro as measured by proliferation and IL-2 secretion
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• unlike Tg(Tcra2D2,Tcrb2D2)1Kuch mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in CD4+ T cells stimulated with anti-CD3
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• under nonpolarizing conditions
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• in CD4+ T cells under nonpolarizing conditions
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• in CD4+ T cells stimulated with MOG35-55 compared with cells from wild-type control but not as much as in cells from Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
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• in CD4+ T cells stimulated with MOG35-55 compared with cells from wild-type control but not as much as in cells from Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
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• IL2 levels from CD4+ T cells stimulated with MOG35-55 do not persist as long as in cells from wild-type mice
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• in CD4+ T cells stimulated with MOG35-55 compared with cells from wild-type control but not as much as in cells from Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
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• in CD4+ T cells stimulated with anti-CD3
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• under nonpolarizing conditions
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• in CD4+ T cells stimulated with anti-CD3
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• under Th17 polarizing conditions
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• of CD4+ T cells stimulated with anti-CD3
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• in CD4+ T cells stimulated with MOG35-55, rested then restimulated with MOG35-55 compared with cells from wild-type control and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
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• under nonpolarizing conditions, Th1 cells are reduced 50% compared to in wild-type but are 3-fold higher than in Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
• in T cells cultures stimulated with MOG35-55
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• 50% under Th17 polarizing conditions compared with wild-type control and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
• in T cells cultures stimulated with MOG35-55
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• under Th2 polarizing conditions compared with wild-type controls and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
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• in CD4+ T cells under nonpolarizing conditions
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• in CD4+ T cells stimulated with MOG35-55 compared with cells from wild-type control and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
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• IL10 levels in T cells stimulated with MOG35-55 rise and contract unlike in cells from wild-type control and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice where levels continue to rise
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• in CD4+ T cells stimulated with MOG35-55 compared with cells from wild-type control and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
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• IL2 levels from T cells stimulated with MOG35-55 do not increase beyond day 1unlike in cells from wild-type control
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• in CD4+ T cells stimulated with MOG35-55 compared with cells from wild-type control and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
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• under Th17 polarizing conditions
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• of CD4+ T cells stimulated with anti-CD3
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• in CD4+ T cells stimulated with MOG35-55, rested then restimulated with MOG35-55 compared with cells from wild-type control and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
|
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• under Th17 polarizing conditions
|
|
• of CD4+ T cells stimulated with anti-CD3
|
|
• in CD4+ T cells stimulated with MOG35-55, rested then restimulated with MOG35-55 compared with cells from wild-type control and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
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• under nonpolarizing conditions, Th1 cells are reduced 50% compared to in wild-type but are 3-fold higher than in Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
• in T cells cultures stimulated with MOG35-55
|
|
• 50% under Th17 polarizing conditions compared with wild-type control and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
• in T cells cultures stimulated with MOG35-55
|
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• under Th2 polarizing conditions compared with wild-type controls and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
|
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 40% of transgenic mice succumb to EAE compared to no non-transgenic littermates
|
|
• 7/15 mice without EAE show typical myelinating/demyelinating lesions of optic neuritis
• mice with EAE show typical myelinating/demyelinating lesions of optic neuritis
• 55 and 78% of transgenic mice immunized with 100 and 10 ug of MOG 35-55 without PT, respectively, develop optic nerve lesions
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• mice with or without EAE that display optic neuritis have myelinating/demyelinating lesions consisting of subpial and endoneurial mononuclear cell infiltrates with demyelination indicated by presence of foamy macrophages
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• mice with optic neuritis have varying degrees of axonal injury and loss
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• CNS tissues show myelin loss
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• mice without EAE develop superficial inflammation around the eyelids; this is unilateral and not observed in wild-type littermates during up to 1 year observation
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• superficial eye lesions in mice without EAE are often associated with progressive atrophy of the eye
• 67% of mutants show these eye lesions compared to no wild-type
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• mice without EAE show eyelid inflammation and eyelid swelling; this is unilateral and not observed in wild-type littermates during up to 1 year observation
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• mice with or without EAE that display optic neuritis have myelinating/demyelinating lesions consisting of subpial and endoneurial mononuclear cell infiltrates with demyelination indicated by presence of foamy macrophages
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• CD4/CD8 single positive ratio in thymus of transgenic mice is biased toward CD4+ compartment
• analysis shows a skewing toward CD4+ T cells in spleens as well
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• spleen cells from naive mice produce high levels of IFN gamma in response to MOG 35-55
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• 4% (3/72) of mice develop spontaneous EAE, indicated initially by a limp tail, followed by hindlimb paralysis between 2.5 and 5 months of age
• 55 and 78% of mice immunized with 100 and 10 ug of MOG 35-55 without PT, respectively, develop optic nerve lesions
• mice with disease have typical myelinating/demyelinating lesions
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• transgenic mice immunized with MOG 35-55 + pertussis toxin (PT) develop more severe EAE than non-transgenic littermates, with earlier onset and greater clinical scores; 50% of mice develop associated optic neuritis also
• injection of PT alone induces clinical EAE in 39% and histological EAE in 56% of transgenics compared to no non-transgenic mice; 80% of mice develop associated optic neuritis also
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• 7/15 mice without EAE show typical myelinating/demyelinating lesions of optic neuritis
• mice with EAE show typical myelinating/demyelinating lesions of optic neuritis
• 55 and 78% of transgenic mice immunized with 100 and 10 ug of MOG 35-55 without PT, respectively, develop optic nerve lesions
|
|
• mice without EAE develop superficial inflammation around the eyelids; this is unilateral and not observed in wild-type littermates during up to 1 year observation
|
|
• CD4/CD8 single positive ratio in thymus of transgenic mice is biased toward CD4+ compartment
• analysis shows a skewing toward CD4+ T cells in spleens as well
|
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• spleen cells from naive mice show increased proliferative response to myelin oligodendrocyte protein peptide 35-55 (MOG 35-55) compared to wild-type mice
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• mice without EAE show eyelid inflammation and eyelid swelling; this is unilateral and not observed in wild-type littermates during up to 1 year observation
|
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• mice without EAE show eyelid inflammation and eyelid swelling; this is unilateral and not observed in wild-type littermates during up to 1 year observation
|
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• mice without EAE show eyelid inflammation and eyelid swelling; this is unilateral and not observed in wild-type littermates during up to 1 year observation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• T cells incubated with LPS-stimulated CD11c+ dendritic cells with IL-23 in the presence of MOG peptide and neutralizing antibodies against IFN-gamma and IL-4 plus either IL-25 or IL-13 antibodies produce less IL-17 than with both IL-25 and IL-13 antibodies or without either
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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 11/12/2024 MGI 6.24 |
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