Phenotypes Associated with This Genotype

Genotype
MGI:5644517

• Allelic Composition: Tg(H2-K^b-Tcra,-Tcrb)1640Kurs/0
• Genetic Background: SJL.FVB-Tg(H2-K^b-Tcra,-Tcrb)1640Kurs

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

Severe infiltration, demyelination, and axonal damage in Tg(H2-K^b-Tcra,-Tcrb)1640Kurs/0 cerebellum and spinal cord

immune system

increased T-helper 1 cell number ( J:149511 )

• Th1 cells are enriched in the CNS more than 2-fold

increased T-helper 17 cell number ( J:149511 )

• Th17 cells are enriched in the CNS 3-fold

abnormal cytokine level ( J:149511 )

• ataxic mice show a higher expression of cytokines in the brain than paralytic relapsed mice

• paralytic relapsed mice show a higher expression of cytokines in the spinal cord than ataxic mice

increased susceptibility to experimental autoimmune encephalomyelitis ( J:149511 )

• mice develop spontaneous experimental autoimmune encephalomyelitis (EAE) at high frequency

• in the eight backcross generation to SJL/J, more than 80% of females, and more than 60% of males, develop EAE within 160 days

• typically, EAE starts with relapsing-remitting (RR) in females, with the first attacks often resolving completely, followed by further bouts

• in a set of mice, the initial bout is dominated by ataxia, with affected mice unable to walk along a straight line, deviating and falling to the side, but not showing limb weakness or paralysis

• in many cases, mice recover completely until a first relapse, commonly showing hind limb paralysis

• later disease episodes mainly show classical paralytic EAE

• RR disease is more common in females than males

• minority of females develop progressive EAE from the beginning whereas, more than 50% of males develop primary progressive EAE

• EAE lesions show prominent deposits of Ig and some activated complement

• mice treated with anti-CD20 antibody to deplete B cells, show suppression of RR-EAE when started at young age

increased autoantibody level ( J:149511 )

• mice produce anti-MOG autoantibodies of endogenous Igh^b allotype; anti-MOG Igs are mainly IgG1 and IgG2a/b isotypes, with very little IgM

• autoantibodies are seen from 5 weeks of life and persist up to 9-10 weeks

CNS inflammation ( J:149511 )

• inflamed CNS tissue contains CD4+ and CD8+ lymphocytes and substantial numbers of B cells expressing CD19 or B220

• inflammatory regions are characterized by numerous CD3+ T cells in the middle of Mac3+ activated macrophage-like cells and are embedded in large areas of demyelination and axon destruction

• most CD4+ T cells infiltrating the CNS are activated

brain inflammation ( J:149511 )

• ataxic mice exhibit large inflammatory and demyelinated lesions in cerebellum and brain stem

• mice showing conventional EAE exhibit lesions distributed throughout the spinal cord, brain stem, and optic nerve

nervous system

CNS inflammation ( J:149511 )

• inflamed CNS tissue contains CD4+ and CD8+ lymphocytes and substantial numbers of B cells expressing CD19 or B220

• inflammatory regions are characterized by numerous CD3+ T cells in the middle of Mac3+ activated macrophage-like cells and are embedded in large areas of demyelination and axon destruction

• most CD4+ T cells infiltrating the CNS are activated

brain inflammation ( J:149511 )

• ataxic mice exhibit large inflammatory and demyelinated lesions in cerebellum and brain stem

• mice showing conventional EAE exhibit lesions distributed throughout the spinal cord, brain stem, and optic nerve

demyelination ( J:149511 )

• ataxic mice exhibit large inflammatory and demyelinated lesions in cerebellum and brain stem

behavior/neurological

ataxia ( J:149511 )

• in a set of mice, the initial bout of autoimmune encephalomyelitis is seen as ataxia

limb paralysis ( J:149511 )

• seen in relapsing mice and in later disease episodes

hematopoietic system

increased T-helper 1 cell number ( J:149511 )

• Th1 cells are enriched in the CNS more than 2-fold

increased T-helper 17 cell number ( J:149511 )

• Th17 cells are enriched in the CNS 3-fold

homeostasis/metabolism

abnormal cytokine level ( J:149511 )

• ataxic mice show a higher expression of cytokines in the brain than paralytic relapsed mice

• paralytic relapsed mice show a higher expression of cytokines in the spinal cord than ataxic mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
multiple sclerosis		DOID:2377	OMIM:612594 OMIM:612595 OMIM:612596	J:149511