Phenotypes associated with this allele

• Allele Symbol: H2^u
• Allele Name: u variant
• Allele ID: MGI:3834991
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	H2^u/H2^u Tg(TCRA)B1Jg/0	B10.PL-H2^u H2-T18^a/(73NS)Sn-Tg(TCRA)B1Jg/J	MGI:3835050
cx2	H2^u/H2^u Tg(TCRA)B1Jg/0 Tg(TCRB)C14Jg/0	B10.PL-H2^u H2-T18^a/(73NS)Sn-Tg(TCRA)B1Jg Tg(TCRB)C14Jg	MGI:3835052
cx3	H2^u/H2^u Tg(TCRB)C14Jg/0	B10.PL-H2^u H2-T18^a/(73NS)Sn-Tg(TCRB)C14Jg/J	MGI:3835051
cx4	H2^u/H2^u Rag1^tm1Mom/Rag1^tm1Mom Tg(Tcra19,Tcrb19)#Stl/0	either: (involves: 129S7/SvEvBrd * C57BL/6 * PL/J) or (involves: 129S7/SvEvBrd * C57BL/6 * C57BL/10 * PL/J)	MGI:6305814
cx5	H2^u/H2^u Tg(Tcra19,Tcrb19)#Stl/0	either: (involves: C57BL/6 * PL/J) or (involves: C57BL/6 * C57BL/10 * PL/J)	MGI:6305810
cx6	H2^u/H2^u Tg(TCRA)B1Jg/? Tg(TCRB)C14Jg/?	involves: C57BL/6 * C57BL/10SnSg * DBA/2 * PL/J	MGI:3835028

Genotype
MGI:3835050

cx1

• Allelic Composition: H2^u/H2^u; Tg(TCRA)B1Jg/0
• Genetic Background: B10.PL-H2^u H2-T18^a/(73NS)Sn-Tg(TCRA)B1Jg/J

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

hematopoietic system

abnormal thymus cell ratio ( J:92992 )

• the ratio of double negative to double-positive thymocytes is significantly higher (0.281) in these mice than in controls (0.016)

decreased thymocyte number ( J:92992 )

• thymus cellularity is reduced by 4 fold compared to controls

increased T cell derived lymphoma incidence ( J:92992 )

• 12.5 % of mice develop lymphoma characterized by CD8⁺CD4^hi-low T cells

• the lymphoma is metastatic and transplantable

increased double-negative T cell number ( J:92992 )

• double-negative thymocyte numbers are increased to 17.2% of all thymocytes from 1.2% in controls

• the absolute number of double negative thymocytes is increased despite reduced thymus cellularity

decreased double-positive T cell number ( J:92992 )

• double-positive thymocyte numbers are decreased to 61.8% of all thymocytes compared to 75.3% for controls

decreased CD4-positive, alpha-beta T cell number ( J:92992 )

• the absolute number of single-positive CD4 thymocytes is decreased

immune system

abnormal thymus cell ratio ( J:92992 )

• the ratio of double negative to double-positive thymocytes is significantly higher (0.281) in these mice than in controls (0.016)

decreased thymocyte number ( J:92992 )

• thymus cellularity is reduced by 4 fold compared to controls

increased T cell derived lymphoma incidence ( J:92992 )

• 12.5 % of mice develop lymphoma characterized by CD8⁺CD4^hi-low T cells

• the lymphoma is metastatic and transplantable

increased double-negative T cell number ( J:92992 )

• double-negative thymocyte numbers are increased to 17.2% of all thymocytes from 1.2% in controls

• the absolute number of double negative thymocytes is increased despite reduced thymus cellularity

decreased double-positive T cell number ( J:92992 )

• double-positive thymocyte numbers are decreased to 61.8% of all thymocytes compared to 75.3% for controls

decreased CD4-positive, alpha-beta T cell number ( J:92992 )

• the absolute number of single-positive CD4 thymocytes is decreased

neoplasm

increased T cell derived lymphoma incidence ( J:92992 )

• 12.5 % of mice develop lymphoma characterized by CD8⁺CD4^hi-low T cells

• the lymphoma is metastatic and transplantable

endocrine/exocrine glands

abnormal thymus cell ratio ( J:92992 )

• the ratio of double negative to double-positive thymocytes is significantly higher (0.281) in these mice than in controls (0.016)

decreased thymocyte number ( J:92992 )

• thymus cellularity is reduced by 4 fold compared to controls

increased T cell derived lymphoma incidence ( J:92992 )

• 12.5 % of mice develop lymphoma characterized by CD8⁺CD4^hi-low T cells

• the lymphoma is metastatic and transplantable

Genotype
MGI:3835052

cx2

• Allelic Composition: H2^u/H2^u; Tg(TCRA)B1Jg/0; Tg(TCRB)C14Jg/0
• Genetic Background: B10.PL-H2^u H2-T18^a/(73NS)Sn-Tg(TCRA)B1Jg Tg(TCRB)C14Jg

immune system

abnormal thymus cell ratio ( J:92992 )

• the ratio of double negative to double-positive thymocytes is significantly higher (0.483) in these mice than in controls (0.016)

• the ratio of single-positive (both CD4⁺ and CD8⁺) thymocytes to double-positive thymocytes is significantly increased

increased T cell derived lymphoma incidence ( J:92992 )

• 21.9 % of mice develop lymphoma characterized by CD8⁺CD4^hi-low T cells

• the lymphoma is metastatic and transplantable

• the lymphoma is not found in mice younger than 80 days of age and occurs with equal frequency to male and female mice

abnormal double-negative T cell morphology ( J:92992 )

• a greater proportion of the double-negative thymocytes present in E16 and E17 thymi are in the most mature (c-kit^-CD44^-CD25^-) stage compared to controls

increased double-negative T cell number ( J:92992 )

• double-negative thymocyte numbers are increased to 11.7% of all thymocytes from 1.2% in controls

• the absolute number of double-negative thymocytes is increased over wild-type and is twice that found in Tg(TCRA)B1Jg transgenic mice

abnormal double-positive T cell morphology ( J:92992 )

• the appearance of double-positive T cells in the thymus first occurs on E16 compared to E17 for controls

decreased double-positive T cell number ( J:92992 )

• the appearance of double-positive T cells in the thymus first occurs on E16 compared to E17 for controls

increased CD4-positive, alpha-beta T cell number ( J:92992 )

• the percentage and absolute number of single-positive CD4 thymocytes is increased

absent gamma-delta T cells ( J:92992 )

• gamma-delta T cells are not detected in the thymus of E18 mice

neoplasm

increased T cell derived lymphoma incidence ( J:92992 )

• 21.9 % of mice develop lymphoma characterized by CD8⁺CD4^hi-low T cells

• the lymphoma is metastatic and transplantable

• the lymphoma is not found in mice younger than 80 days of age and occurs with equal frequency to male and female mice

hematopoietic system

abnormal thymus cell ratio ( J:92992 )

• the ratio of double negative to double-positive thymocytes is significantly higher (0.483) in these mice than in controls (0.016)

• the ratio of single-positive (both CD4⁺ and CD8⁺) thymocytes to double-positive thymocytes is significantly increased

increased T cell derived lymphoma incidence ( J:92992 )

• 21.9 % of mice develop lymphoma characterized by CD8⁺CD4^hi-low T cells

• the lymphoma is metastatic and transplantable

• the lymphoma is not found in mice younger than 80 days of age and occurs with equal frequency to male and female mice

abnormal double-negative T cell morphology ( J:92992 )

• a greater proportion of the double-negative thymocytes present in E16 and E17 thymi are in the most mature (c-kit^-CD44^-CD25^-) stage compared to controls

increased double-negative T cell number ( J:92992 )

• double-negative thymocyte numbers are increased to 11.7% of all thymocytes from 1.2% in controls

• the absolute number of double-negative thymocytes is increased over wild-type and is twice that found in Tg(TCRA)B1Jg transgenic mice

abnormal double-positive T cell morphology ( J:92992 )

• the appearance of double-positive T cells in the thymus first occurs on E16 compared to E17 for controls

decreased double-positive T cell number ( J:92992 )

• the appearance of double-positive T cells in the thymus first occurs on E16 compared to E17 for controls

increased CD4-positive, alpha-beta T cell number ( J:92992 )

• the percentage and absolute number of single-positive CD4 thymocytes is increased

absent gamma-delta T cells ( J:92992 )

• gamma-delta T cells are not detected in the thymus of E18 mice

endocrine/exocrine glands

abnormal thymus cell ratio ( J:92992 )

• the ratio of double negative to double-positive thymocytes is significantly higher (0.483) in these mice than in controls (0.016)

• the ratio of single-positive (both CD4⁺ and CD8⁺) thymocytes to double-positive thymocytes is significantly increased

increased T cell derived lymphoma incidence ( J:92992 )

• 21.9 % of mice develop lymphoma characterized by CD8⁺CD4^hi-low T cells

• the lymphoma is metastatic and transplantable

• the lymphoma is not found in mice younger than 80 days of age and occurs with equal frequency to male and female mice

Genotype
MGI:3835051

cx3

• Allelic Composition: H2^u/H2^u; Tg(TCRB)C14Jg/0
• Genetic Background: B10.PL-H2^u H2-T18^a/(73NS)Sn-Tg(TCRB)C14Jg/J

immune system

abnormal double-negative T cell morphology ( J:92992 )

• a greater proportion of the double-negative thymocytes present in E16 and E17 thymi are in the most mature (c-kit^-CD44^-CD25^-) stage compared to controls

abnormal double-positive T cell morphology ( J:92992 )

• the appearance of double-positive T cells in the thymus first occurs on E15 compared to E17 for controls

absent gamma-delta T cells ( J:92992 )

• gamma-delta T cells are not detected in the thymus of E18 mice

hematopoietic system

abnormal double-negative T cell morphology ( J:92992 )

• a greater proportion of the double-negative thymocytes present in E16 and E17 thymi are in the most mature (c-kit^-CD44^-CD25^-) stage compared to controls

abnormal double-positive T cell morphology ( J:92992 )

• the appearance of double-positive T cells in the thymus first occurs on E15 compared to E17 for controls

absent gamma-delta T cells ( J:92992 )

• gamma-delta T cells are not detected in the thymus of E18 mice

Genotype
MGI:6305814

cx4

• Allelic Composition: H2^u/H2^u; Rag1^tm1Mom/Rag1^tm1Mom; Tg(Tcra19,Tcrb19)#Stl/0
• Genetic Background: either: (involves: 129S7/SvEvBrd * C57BL/6 * PL/J) or (involves: 129S7/SvEvBrd * C57BL/6 * C57BL/10 * PL/J)

immune system

increased susceptibility to autoimmune disorder ( J:19795 )

• 100% of mice develop spontaneous autoimmune encephalomyelitis within 12 months

• onset and rate of progression of disease varies, with an average age of onset of 13 weeks

• cerebellum and spinal cord exhibit patchy lesions with mononuclear cell infiltrates

• activated myelin basic protein (MBP)-specific T cells are found in the brain but not in the peripheral lymphoid tissues

behavior/neurological

limb paralysis ( J:19795 )

• weakness or paralysis of the hind legs is seen first and then extends to the front legs

• once hind legs are completely paralyzed, the disease progresses very rapidly

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
multiple sclerosis		DOID:2377	OMIM:612594 OMIM:612595 OMIM:612596	J:19795

Genotype
MGI:6305810

cx5

• Allelic Composition: H2^u/H2^u; Tg(Tcra19,Tcrb19)#Stl/0
• Genetic Background: either: (involves: C57BL/6 * PL/J) or (involves: C57BL/6 * C57BL/10 * PL/J)

immune system

increased susceptibility to autoimmune disorder ( J:19795 )

• about 11% and 14% of mice develop spontaneous autoimmune encephalomyelitis within 6 months and 12 months, respectively

increased susceptibility to experimental autoimmune encephalomyelitis ( J:19795 )

• all mice develop a rapidly progressing form of experimental autoimmune encephalomyelitis after immunization with myelin basic protein (MBP)

Genotype
MGI:3835028

cx6

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

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