Mouse Genome Informatics
cx1
    Mogtm1(cre)Gkl/Mogtm1(cre)Gkl
Tg(Tcra2D2,Tcrb2D2)1Kuch/0

C57BL/6-Mogtm1(cre)Gkl Tg(Tcra2D2,Tcrb2D2)1Kuch
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• between 15% and 20% of mice develop spontaneous EAE

Mouse Models of Human Disease
OMIM IDRef(s)
Multiple Sclerosis, Susceptibility To; MS 126200 J:151335


Mouse Genome Informatics
cx2
    Igh-Jtm1Aigl/Igh-J+
Mogtm1Dpd/Mogtm1Dpd
Tg(Tcra2D2,Tcrb2D2)1Kuch/0

involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• disease started between 7 and 10 weeks of age, with classical paralytic EAE signs

muscle
• in a minority of cases, with a spastic component

nervous system
• 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

vision/eye
• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in optic nerve

immune system
• inflammatory infiltrates in the trigeminal ganglia, spinal ganglia, spinal roots despite the absence of MOG within these tissues

Mouse Models of Human Disease
OMIM IDRef(s)
Multiple Sclerosis, Susceptibility To; MS 126200 J:151335


Mouse Genome Informatics
cx3
    Igh-Jtm1Aigl/Igh-J+
Tg(Tcra2D2,Tcrb2D2)1Kuch/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• disease started between 7 and 10 weeks of age, with classical paralytic EAE signs

immune system
• fifty percent spontaneously develop opticospinal myelitis
• inflammatory infiltrates in the trigeminal ganglia, spinal ganglia, spinal roots despite the absence of MOG within these tissues

muscle
• in a minority of cases, with a spastic component

nervous system
• 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

vision/eye
• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in optic nerve

Mouse Models of Human Disease
OMIM IDRef(s)
Multiple Sclerosis, Susceptibility To; MS 126200 J:151335


Mouse Genome Informatics
cx4
    Pdcd1tm1Hon/Pdcd1tm1Hon
Tg(Tcra2D2,Tcrb2D2)1Kuch/0

involves: 129S2/SvPas
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• 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


Mouse Genome Informatics
cx5
    Mogtm1Dpd/Mogtm1Dpd
Tg(Tcra2D2,Tcrb2D2)1Kuch/0

involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• disease started between 7 and 10 weeks of age, with classical paralytic EAE signs

immune system
• 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

muscle
• in a minority of cases, with a spastic component

nervous system
• 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

vision/eye
• lesions consisting of lymphocytic infiltration, demyelation and axonal damage in optic nerve

Mouse Models of Human Disease
OMIM IDRef(s)
Multiple Sclerosis, Susceptibility To; MS 126200 J:151335


Mouse Genome Informatics
cx6
    Mogtm1Dpd/Mogtm1Dpd
Rag2tm1Cgn/Rag2tm1Cgn
Tg(Tcra2D2,Tcrb2D2)1Kuch/0

involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• spontaneous EAE develops in two out of six mice

Mouse Models of Human Disease
OMIM IDRef(s)
Multiple Sclerosis, Susceptibility To; MS 126200 J:151335


Mouse Genome Informatics
cx7
    H2-T23tm2Cant/H2-T23tm2Cant
Tg(Tcra2D2,Tcrb2D2)1Kuch/?

involves: 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• 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
• 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

hematopoietic system
• 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


Mouse Genome Informatics
cx8
    H2-T23tm3Cant/H2-T23tm3Cant
Tg(Tcra2D2,Tcrb2D2)1Kuch/?

involves: 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• CD4 T cells are fully resistant to suppression by CD8 T regulatory cells in vitro as measured by proliferation and IL-2 secretion

hematopoietic system
• CD4 T cells are fully resistant to suppression by CD8 T regulatory cells in vitro as measured by proliferation and IL-2 secretion


Mouse Genome Informatics
cx9
    Tigittm1Sdl/Tigittm1Sdl
Tg(Tcra2D2,Tcrb2D2)1Kuch/0

involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system


Mouse Genome Informatics
cx10
    Cd5tm1.1Chra/Cd5tm1.1Chra
Tg(Tcra2D2,Tcrb2D2)1Kuch/0

involves: C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• under nonpolarizing conditions
• in CD4+ T cells stimulated with anti-CD3
• in CD4+ T cells under nonpolarizing conditions
• 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
• 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
• IL2 levels from CD4+ T cells stimulated with MOG35-55 do not persist as long as in cells from wild-type mice
• 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

hematopoietic system
• under nonpolarizing conditions
• in CD4+ T cells stimulated with anti-CD3


Mouse Genome Informatics
tg11
    Tg(Tcra2D2,Tcrb2D2)1Kuch/0
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• under Th17 polarizing conditions
• 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
• under Th2 polarizing conditions compared with wild-type controls and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
• 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
• in CD4+ T cells under nonpolarizing conditions
• in CD4+ T cells stimulated with MOG35-55 compared with cells from wild-type control and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
• 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
• in CD4+ T cells stimulated with MOG35-55 compared with cells from wild-type control and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
• IL2 levels from T cells stimulated with MOG35-55 do not increase beyond day 1unlike in cells from wild-type control
• in CD4+ T cells stimulated with MOG35-55 compared with cells from wild-type control and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice

cellular
• under Th17 polarizing conditions

hematopoietic system
• under Th17 polarizing conditions
• 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
• under Th2 polarizing conditions compared with wild-type controls and Cd5tm1Cgn/Cd5tm1Cgn Tg(Tcra2D2,Tcrb2D2)1Kuch mice
• 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


Mouse Genome Informatics
tg12
    Tg(Tcra2D2,Tcrb2D2)1Kuch/0
involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 40% of transgenic mice succumb to EAE compared to no non-transgenic littermates

nervous system
• 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 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
• mice with optic neuritis have varying degrees of axonal injury and loss
• CNS tissues show myelin loss

vision/eye
• 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
• 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
• 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
• 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

immune system
• 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
• spleen cells from naive mice produce high levels of IFN gamma in response to MOG 35-55
• 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
• 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
• 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

hematopoietic system
• 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

cellular
• spleen cells from naive mice show increased proliferative response to myelin oligodendrocyte protein peptide 35-55 (MOG 35-55) compared to wild-type mice

homeostasis/metabolism
• EAE-affected mice showed edema in the brain and spinal cord
• 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


Mouse Genome Informatics
tg13
    Tg(Tcra2D2,Tcrb2D2)1Kuch/?
involves: C57BL/6 * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• 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