Phenotypes Associated with This Genotype

Genotype
MGI:3835028

• Allelic Composition: H2^u/H2^u; Tg(TCRA)B1Jg/?; Tg(TCRB)C14Jg/?
• Genetic Background: involves: C57BL/6 * C57BL/10SnSg * DBA/2 * PL/J

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

immune system

decreased double-positive T cell number ( J:92991 )

• the double-positive population in the thymus is reduced by almost half

abnormal effector T cell morphology ( J:92991 )

• majority of mice have CD4 T cells expressing the transgenic TCR

• however, in some mice T cells expressing the transgenic TCR do not mature

• in other mice, transgenic T cell mature but fail to express the CD4 coreceptor

increased CD4-positive, alpha-beta T cell number ( J:92991 )

• there is about a 3-fold increase in the percentage of CD4 single-positive thymoyctes compared to wild-type controls

• CD4 T cells numbers are also significantly increased in the spleen

decreased CD8-positive, alpha-beta T cell number ( J:92991 )

• decreased CD8-positive T cells are found in the spleen

• there is also a decrease in CD8 single-positive thymocytes

abnormal CD4-positive, alpha-beta T cell physiology ( J:92991 )

• CD4 T cells proliferate strongly and secrete cytokines in response to peptide from the first 20 amino acids of myelin basic protein (MBP) displayed in the context of H2^u

increased susceptibility to experimental autoimmune encephalomyelitis ( J:92991 )

• mice are much more susceptible to experimental autoimmune encephalomyelitis induced by MBP immunization

• 29 of 32 mice develop EAE after induction with MBP-adjuvant compared to 10 of 28 for controls

• severity of EAE in transgenic mice is greater than controls

• EAE could also be induced by administration of pertussis toxin or LPS in these mice but not in controls

• a small percentage of mice develop spontaneous EAE

increased autoantibody level ( J:92991 )

• immunization with MBP peptide leads to about a 100-fold higher levels of anti-MBP antibodies compared to immunized wild-type mice

behavior/neurological

paralysis ( J:92991 )

• spontaneous experimental autoimmune encephalomyelitis (EAE) can occur in these mice when housed under non-sterile conditions

• 12 mice within a 10 month period developed hind limb paralysis

• this paralysis was associated with infiltrates into the spinal cord white matter

• between 14 and 44% of mice develop a limp tail during a 4 week window starting at six weeks of age

• some of these mice progress to a hind limb paralysis

• transgenic mice kept in a germ-free facility did not develop this spontaneous EAE

hematopoietic system

decreased double-positive T cell number ( J:92991 )

• the double-positive population in the thymus is reduced by almost half

abnormal effector T cell morphology ( J:92991 )

• majority of mice have CD4 T cells expressing the transgenic TCR

• however, in some mice T cells expressing the transgenic TCR do not mature

• in other mice, transgenic T cell mature but fail to express the CD4 coreceptor

increased CD4-positive, alpha-beta T cell number ( J:92991 )

• there is about a 3-fold increase in the percentage of CD4 single-positive thymoyctes compared to wild-type controls

• CD4 T cells numbers are also significantly increased in the spleen

decreased CD8-positive, alpha-beta T cell number ( J:92991 )

• decreased CD8-positive T cells are found in the spleen

• there is also a decrease in CD8 single-positive thymocytes

abnormal CD4-positive, alpha-beta T cell physiology ( J:92991 )

• CD4 T cells proliferate strongly and secrete cytokines in response to peptide from the first 20 amino acids of myelin basic protein (MBP) displayed in the context of H2^u

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
multiple sclerosis		DOID:2377	OMIM:612594 OMIM:612595 OMIM:612596	J:92991