All Phenotypes H2-Ab1<b-tm1Gru> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

H2-Ab1^b-tm1Gru
targeted mutation 1, Michael J Grusby
MGI:2158420

Summary

25 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru	B6.129S2-H2-Ab1^b-tm1Gru	MGI:3835151
hm2	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru	involves: 129S2/SvPas	MGI:3813928
hm3	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru	involves: 129S2/SvPas * C57BL/6	MGI:3844893
hm4	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru	involves: 129S2/SvPas * C57BL/6J	MGI:2386116
hm5	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru	NOD.129S2-H2-Ab1^b-tm1Gru	MGI:3623978
cn6	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Runx1^tm1Toku/Runx1^tm1Toku Runx3^tm1Itan/Runx3^tm1Itan Tg(Cd4-cre)1Cwi/0	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * DBA/2	MGI:3776115
cx7	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(Ab1TL)1Gru/0	B6.Cg-H2-Ab1^b-tm1Gru Tg(Ab1TL)1Gru	MGI:3835149
cx8	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)1Dv/0 Tg(Ins2-CD80)3B7Flv/0	B6.Cg-H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)1Dv Tg(Ins2-CD80)3B7Flv	MGI:3623405
cx9	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Themis^tm1Lov/Themis^tm1Lov	involves: 129	MGI:4353390
cx10	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tespa1^tm1Smoc/Tespa1^tm1Smoc	involves: 129 * 129S2/SvPas * C57BL/6	MGI:5432922
cx11	Cd8a^tm1Asin/Cd8a^tm1Asin Cd8b1^tm1Litt/Cd8b1^tm1Litt H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru	involves: 129 * FVB/N	MGI:3760624
cx12	Rr96^tm1.1Yzo/Rr96^tm1.1Yzo H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru	involves: 129P2/OlaHsd * 129S2/SvPas	MGI:3808861
cx13	Rr94^tm3.2Litt/Rr94^tm3.2Litt H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru	involves: 129P2/OlaHsd * 129S2/SvPas * FVB/N	MGI:4452092
cx14	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)1Dv/0 Tg(Ins2-CD80)3B7Flv/0	involves: 129S2/SvPas * C57BL/6 * C57BL/10SnJ * CBA	MGI:3639135
cx15	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)1Dv/0 Tg(HLA-DRB1)31Dmz/0 Tg(Ins2-CD80)3B7Flv/0	involves: 129S2/SvPas * C57BL/6 * C57BL/10SnJ * CBA * SJL	MGI:3639133
cx16	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(Ins2-CD80)3B7Flv/0	involves: 129S2/SvPas * C57BL/6 * CBA	MGI:3639140
cx17	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(HLA-DRB1)31Dmz/0 Tg(Ins2-CD80)3B7Flv/0	involves: 129S2/SvPas * C57BL/6 * CBA * SJL	MGI:3639130
cx18	B2m^tm1Unc/B2m^tm1Unc H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell	NOD.Cg-B2m^tm1Unc H2-Ab1^b-tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell	MGI:3687124
cx19	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell	NOD.Cg-H2-Ab1^b-tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell	MGI:3623997
cx20	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(CD4,HLA-DQA1,HLA-DQB1)N8Ell/Tg(CD4,HLA-DQA1,HLA-DQB1)N8Ell	NOD.Cg-H2-Ab1^b-tm1Gru Tg(CD4,HLA-DQA1,HLA-DQB1)N8Ell	MGI:3687137
cx21	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)70Myl/0	NOD.Cg-H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)70Myl	MGI:3687027
cx22	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)73Myl/0	NOD.Cg-H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)73Myl	MGI:3687026
cx23	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Ighm^tm1Cgn/Ighm^tm1Cgn Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell	NOD.Cg-Ighm^tm1Cgn H2-Ab1^b-tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell	MGI:3687129
cx24	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Rag1^tm1Mom/Rag1^tm1Mom Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell	NOD.Cg-Rag1^tm1Mom H2-Ab1^b-tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell	MGI:3687126
cx25	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Rag1^tm1Mom/Rag1^tm1Mom Tg(HLA-DQA1,HLA-DQB1)73Myl/0	NOD.Cg-Rag1^tm1Mom H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)73Myl	MGI:3687028

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru
Genetic Background	B6.129S2-H2-Ab1^b-tm1Gru

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)

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

immune system

decreased CD4-positive, alpha-beta T cell number ( J:91341 )

• CD4 T cells are virtually absent in these mice with only a few detectable in the periphery

abnormal lymphocyte physiology ( J:91341 )

• lymphocytes fail to proliferate in response to restimulation with bovine insulin antigen

abnormal B cell physiology ( J:91341 )

• B cells fail to adhere to surfaces coated with anti-MHC II antibodies

hematopoietic system

decreased CD4-positive, alpha-beta T cell number ( J:91341 )

• CD4 T cells are virtually absent in these mice with only a few detectable in the periphery

abnormal lymphocyte physiology ( J:91341 )

• lymphocytes fail to proliferate in response to restimulation with bovine insulin antigen

abnormal B cell physiology ( J:91341 )

• B cells fail to adhere to surfaces coated with anti-MHC II antibodies

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru
Genetic Background	involves: 129S2/SvPas

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)

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

cardiovascular system

abnormal artery development ( J:134875 )

• mice exhibit impaired arteriogenesis following occlusion compared to in similarly treated wild-type mice

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru
Genetic Background	involves: 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)

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

immune system

decreased CD4-positive, alpha-beta T cell number ( J:67941 )

• peripheral CD4⁺ T cell numbers are reduced more than 10-fold

decreased single-positive T cell number ( J:67941 )

• CD4 single-positive thymocyte numbers are decreased to 2.1% of thymocytes compared to 7.6% in wild-type controls

decreased IgG1 level ( J:67941 )

• mice fail to produce measurable antigen specific IgG1 levels in response to T cell dependent antigens even after two doses

decreased IgM level ( J:67941 )

• mice fail to produce measurable antigen specific IgM levels in response to T cell dependent antigens

abnormal level of surface class II molecules ( J:67941 )

• MHC II complex is not expressed on the surface of cells

hematopoietic system

decreased CD4-positive, alpha-beta T cell number ( J:67941 )

• peripheral CD4⁺ T cell numbers are reduced more than 10-fold

decreased single-positive T cell number ( J:67941 )

• CD4 single-positive thymocyte numbers are decreased to 2.1% of thymocytes compared to 7.6% in wild-type controls

decreased IgG1 level ( J:67941 )

• mice fail to produce measurable antigen specific IgG1 levels in response to T cell dependent antigens even after two doses

decreased IgM level ( J:67941 )

• mice fail to produce measurable antigen specific IgM levels in response to T cell dependent antigens

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru
Genetic Background	involves: 129S2/SvPas * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)

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

immune system

decreased CD4-positive, alpha-beta T cell number ( J:74418 )

• CD4+ T cell count is reduced in the periphery relative to controls, but there are reduced but detectable numbers (3.2%) in the thymus

increased CD8-positive, alpha-beta T cell number ( J:74418 )

• mice show elevated single-positive CD8+ T cells in the thymus and periphery relative to controls

abnormal humoral immune response ( J:74418 )

• mutants do not mount a complete immune response to an antigen such as TNP-conjugated ovalbumin

decreased IgG level ( J:74418 )

• 12 days post-immunization, mutants have not produced IgG₁, IgG_2a, IgG_2b or IgG₃ specific for TNP

increased IgM level ( J:74418 )

• mutants produce IgM antigen-specific antibodies with consistently higher titers than control littermates

abnormal response to transplant ( J:91742 )

• skin grafts from OVA expressing transgenic mice ( Tg(CAG-OVA)916Jen) are indistinguishable from wild-type donor skin grafts for the first 40 days

• rejection starts occurring after 40 days with 25% of the transgenic grafts being completely lost after 115 days

hematopoietic system

decreased CD4-positive, alpha-beta T cell number ( J:74418 )

• CD4+ T cell count is reduced in the periphery relative to controls, but there are reduced but detectable numbers (3.2%) in the thymus

increased CD8-positive, alpha-beta T cell number ( J:74418 )

• mice show elevated single-positive CD8+ T cells in the thymus and periphery relative to controls

decreased IgG level ( J:74418 )

• 12 days post-immunization, mutants have not produced IgG₁, IgG_2a, IgG_2b or IgG₃ specific for TNP

increased IgM level ( J:74418 )

• mutants produce IgM antigen-specific antibodies with consistently higher titers than control littermates

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru
Genetic Background	NOD.129S2-H2-Ab1^b-tm1Gru

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)

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

immune system

immune system phenotype ( J:86540 )

N	• NOD mice homozygous for this targeted mutation alone show no indication of inflammation at any age

cardiovascular system

cardiovascular system phenotype ( J:86540 )

N	• NOD mice homozygous for this targeted mutation alone show no indication of cardiac enlargement or inflammation at any age

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Runx1^tm1Toku/Runx1^tm1Toku Runx3^tm1Itan/Runx3^tm1Itan Tg(Cd4-cre)1Cwi/0
Genetic Background	involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)
Runx1^tm1Toku mutation (0 available); any Runx1 mutation (34 available)
Runx3^tm1Itan mutation (1 available); any Runx3 mutation (27 available)
Tg(Cd4-cre)1Cwi mutation (12 available)

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

immune system

increased CD4-positive, alpha-beta T cell number ( J:131081 )

• mice have predominance of CD4+CD8- T cells in thymus and periphery, indicating that MHC I-restricted cells are forced to differentiate into CD4+CD8- T cells

abnormal interferon secretion ( J:131081 )

• after TCR stimulation, interferon gamma production is absent from class I-restricted CD4+CD8- cells

hematopoietic system

increased CD4-positive, alpha-beta T cell number ( J:131081 )

• mice have predominance of CD4+CD8- T cells in thymus and periphery, indicating that MHC I-restricted cells are forced to differentiate into CD4+CD8- T cells

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(Ab1TL)1Gru/0
Genetic Background	B6.Cg-H2-Ab1^b-tm1Gru Tg(Ab1TL)1Gru

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)
Tg(Ab1TL)1Gru mutation (1 available)

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

hematopoietic system

abnormal CD4-positive T cell differentiation ( J:91341 )

• CD4⁺ T cell development is normal in these mice

abnormal macrophage antigen presentation ( J:91341 )

• peritoneal macrophages have an impaired capacity to activate I-A^b-restricted T cell hybridomas when loaded with the cognate peptide

immune system

abnormal CD4-positive T cell differentiation ( J:91341 )

• CD4⁺ T cell development is normal in these mice

abnormal professional antigen presenting cell physiology ( J:91341 )

• splenic APC have an impaired capacity to activate I-A^b-restricted T cell hybridomas when loaded with the cognate peptide

• LPS-induced blasts and peritoneal macrophages are also poor stimulators

• these splenic APC are also poor stimulators for freshly isolated T cells collected from immunized mice

• chemically fixed APC are also poor stimulators to T cell hybridomas when cognate peptide is loaded under neutral pH conditions

• however, chemically fixed APC are excellent stimulators when cognate peptide is loaded under acidic (pH 5) conditions

abnormal macrophage antigen presentation ( J:91341 )

• peritoneal macrophages have an impaired capacity to activate I-A^b-restricted T cell hybridomas when loaded with the cognate peptide

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)1Dv/0 Tg(Ins2-CD80)3B7Flv/0
Genetic Background	B6.Cg-H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)1Dv Tg(Ins2-CD80)3B7Flv

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)
Tg(HLA-DQA1,HLA-DQB1)1Dv mutation (5 available)
Tg(Ins2-CD80)3B7Flv mutation (5 available)

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

immune system

salivary gland inflammation ( J:59245 )

• diabetic transgenic mice display sialadenitis

increased susceptibility to autoimmune diabetes ( J:59245 )

• over 80% of transgenic mice develop diabetes (positive urine glucose test and >250 mg/dl blood glucose) beginning at 4 months of age

homeostasis/metabolism

increased circulating glucose level ( J:59245 )

• over 80% have blood glucose levels above 250 mg/dl

increased urine glucose level ( J:59245 )

• seen in over 80% of mice

digestive/alimentary system

salivary gland inflammation ( J:59245 )

• diabetic transgenic mice display sialadenitis

endocrine/exocrine glands

salivary gland inflammation ( J:59245 )

• diabetic transgenic mice display sialadenitis

renal/urinary system

increased urine glucose level ( J:59245 )

• seen in over 80% of mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:59245

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Themis^tm1Lov/Themis^tm1Lov
Genetic Background	involves: 129

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)
Themis^tm1Lov mutation (0 available); any Themis mutation (54 available)

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

immune system

abnormal negative T cell selection ( J:151075 )

• the number of transitional CD4+CD8^int thymocytes is low in these mice when normally MHC-II deficient mice have high numbers of this population

hematopoietic system

abnormal negative T cell selection ( J:151075 )

• the number of transitional CD4+CD8^int thymocytes is low in these mice when normally MHC-II deficient mice have high numbers of this population

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tespa1^tm1Smoc/Tespa1^tm1Smoc
Genetic Background	involves: 129 * 129S2/SvPas * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)
Tespa1^tm1Smoc mutation (1 available); any Tespa1 mutation (33 available)

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

immune system

absent CD4-positive, alpha-beta T cells ( J:186446 )

• in the thymus compared with H2-Ab1^tm1Gru homozygotes

decreased CD8-positive, alpha-beta T cell number ( J:186446 )

• in the thymus compared with H2-Ab1^tm1Gru homozygotes

hematopoietic system

absent CD4-positive, alpha-beta T cells ( J:186446 )

• in the thymus compared with H2-Ab1^tm1Gru homozygotes

decreased CD8-positive, alpha-beta T cell number ( J:186446 )

• in the thymus compared with H2-Ab1^tm1Gru homozygotes

Allelic Composition	Cd8a^tm1Asin/Cd8a^tm1Asin Cd8b1^tm1Litt/Cd8b1^tm1Litt H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru
Genetic Background	involves: 129 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd8a^tm1Asin mutation (0 available); any Cd8a mutation (37 available)
Cd8b1^tm1Litt mutation (1 available); any Cd8b1 mutation (21 available)
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)

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

immune system

decreased CD4-positive, alpha-beta T cell number ( J:126026 )

• these cells are almost absent in the thymus and the lymph nodes

increased CD8-positive, alpha-beta T cell number ( J:126026 )

• 1.6 fold increase in number of these cells in the lymph nodes, compared to mice that have a wild-type allele for Cd8a on this mutant background

hematopoietic system

decreased CD4-positive, alpha-beta T cell number ( J:126026 )

• these cells are almost absent in the thymus and the lymph nodes

increased CD8-positive, alpha-beta T cell number ( J:126026 )

• 1.6 fold increase in number of these cells in the lymph nodes, compared to mice that have a wild-type allele for Cd8a on this mutant background

Allelic Composition	Rr96^tm1.1Yzo/Rr96^tm1.1Yzo H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru
Genetic Background	involves: 129P2/OlaHsd * 129S2/SvPas

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)
Rr96^tm1.1Yzo mutation (0 available); any Rr96 mutation (0 available)

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

immune system

abnormal T cell differentiation ( J:130559 )

• the peripheral CD4⁺CD8⁺ double positive T cells observed in Cd4^tm1.1Yzo homozygotes are also present in these mice demonstrating Class II-independence of this cell population

hematopoietic system

abnormal T cell differentiation ( J:130559 )

• the peripheral CD4⁺CD8⁺ double positive T cells observed in Cd4^tm1.1Yzo homozygotes are also present in these mice demonstrating Class II-independence of this cell population

Allelic Composition	Rr94^tm3.2Litt/Rr94^tm3.2Litt H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru
Genetic Background	involves: 129P2/OlaHsd * 129S2/SvPas * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)
Rr94^tm3.2Litt mutation (0 available); any Rr94 mutation (0 available)

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

immune system

immune system phenotype ( J:158962 )

N	• the expression of CD4 in post-selection thymocytes is normal

abnormal T cell subpopulation ratio ( J:158962 )

• the ratio of CD4 single positive to CD8 single positive T cells is inverted compared to in wild-type mice

decreased CD4-positive, alpha-beta T cell number ( J:158962 )

• mature CD4 single positive and peripheral CD4^lo T cell populations are largely lost unlike in wild-type mice

increased CD8-positive, alpha-beta T cell number ( J:158962 )

• in the thymus

hematopoietic system

abnormal T cell subpopulation ratio ( J:158962 )

• the ratio of CD4 single positive to CD8 single positive T cells is inverted compared to in wild-type mice

decreased CD4-positive, alpha-beta T cell number ( J:158962 )

• mature CD4 single positive and peripheral CD4^lo T cell populations are largely lost unlike in wild-type mice

increased CD8-positive, alpha-beta T cell number ( J:158962 )

• in the thymus

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)1Dv/0 Tg(Ins2-CD80)3B7Flv/0
Genetic Background	involves: 129S2/SvPas * C57BL/6 * C57BL/10SnJ * CBA

Find Mice

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

immune system

increased interferon-gamma secretion ( J:68641 )

• stimulated CD4+ T cells secrete increased levels of Ifng compared to either DR4-transgenic or double transgenic MHC class II-deficient mice

decreased interleukin-6 secretion ( J:68641 )

• stimulated CD4+ T cells secrete low levels of Il-6 compared to either DR4-transgenic or double transgenic MHC class II-deficient mice

increased susceptibility to autoimmune diabetes ( J:68641 )

• 73% of mice expressing the transgene develop diabetes (blood glucose >250 mg/dl) compared to 0% of nontransgenic MHC class II-deficient mice

homeostasis/metabolism

increased circulating glucose level ( J:68641 )

• 73% display blood glucose levels above 250 mg/dl

increased urine glucose level ( J:68641 )

• seen in 73% of mice

renal/urinary system

increased urine glucose level ( J:68641 )

• seen in 73% of mice

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)1Dv/0 Tg(HLA-DRB1)31Dmz/0 Tg(Ins2-CD80)3B7Flv/0
Genetic Background	involves: 129S2/SvPas * C57BL/6 * C57BL/10SnJ * CBA * SJL

Find Mice

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

immune system

salivary gland inflammation ( J:68641 )

• transgenic mice develop sialadenitis and severity is associated with diabetes development

abnormal CD4-positive, alpha beta T cell morphology ( J:68641 )

• coexpression of DR4 and DQ8 transgenes increases CD4+ T cell numbers 2-fold compared to either DR4 or DQ8 single transgenic line

abnormal CD8-positive, alpha beta T cell morphology ( J:68641 )

• there are fewer CD8+ T cells in pancreatic infiltrates than in MHC class II-deficient mice expressing only DQ8

decreased susceptibility to autoimmune diabetes ( J:68641 )

• incidence of diabetes (blood glucose >250 mg/dl; 5/22, 23%) is lowered from incidence in MHC class II-deficient mice expressing the DQ8 transgene (73%) and similar to deficient mice transgenic for DR4

endocrine/exocrine glands

salivary gland inflammation ( J:68641 )

• transgenic mice develop sialadenitis and severity is associated with diabetes development

hematopoietic system

abnormal CD4-positive, alpha beta T cell morphology ( J:68641 )

• coexpression of DR4 and DQ8 transgenes increases CD4+ T cell numbers 2-fold compared to either DR4 or DQ8 single transgenic line

abnormal CD8-positive, alpha beta T cell morphology ( J:68641 )

• there are fewer CD8+ T cells in pancreatic infiltrates than in MHC class II-deficient mice expressing only DQ8

digestive/alimentary system

salivary gland inflammation ( J:68641 )

• transgenic mice develop sialadenitis and severity is associated with diabetes development

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:68641

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(Ins2-CD80)3B7Flv/0
Genetic Background	involves: 129S2/SvPas * C57BL/6 * CBA

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)
Tg(Ins2-CD80)3B7Flv mutation (5 available)

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

immune system

decreased susceptibility to autoimmune diabetes ( J:68641 )

• only one of the MHC class II-deficient mice developed diabetes (blood glucose >250 mg/dl)

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(HLA-DRB1)31Dmz/0 Tg(Ins2-CD80)3B7Flv/0
Genetic Background	involves: 129S2/SvPas * C57BL/6 * CBA * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)
Tg(HLA-DRB1)31Dmz mutation (1 available)
Tg(Ins2-CD80)3B7Flv mutation (5 available)

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

endocrine/exocrine glands

salivary gland inflammation ( J:68641 )

• transgenic mice develop sialadenitis and severity is associated with diabetes development

immune system

salivary gland inflammation ( J:68641 )

• transgenic mice develop sialadenitis and severity is associated with diabetes development

abnormal CD4-positive, alpha beta T cell morphology ( J:68641 )

• expression of the DR4 transgene increases CD4+ T cell numbers compared to the H2-Ab1-deficient Tg(Ins2-CD80)3B7Flv mice

abnormal CD8-positive, alpha beta T cell morphology ( J:68641 )

• there are fewer CD8+ T cells in pancreatic infiltrates than in MHC class II-deficient mice expressing only DQ8

decreased susceptibility to autoimmune diabetes ( J:68641 )

• incidence of diabetes (5/20) is lower than in MHC class II-deficient mice expressing the DQ8 transgene where incidence is 3-fold higher (73%)

hematopoietic system

abnormal CD4-positive, alpha beta T cell morphology ( J:68641 )

• expression of the DR4 transgene increases CD4+ T cell numbers compared to the H2-Ab1-deficient Tg(Ins2-CD80)3B7Flv mice

abnormal CD8-positive, alpha beta T cell morphology ( J:68641 )

• there are fewer CD8+ T cells in pancreatic infiltrates than in MHC class II-deficient mice expressing only DQ8

digestive/alimentary system

salivary gland inflammation ( J:68641 )

• transgenic mice develop sialadenitis and severity is associated with diabetes development

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:68641

Allelic Composition	B2m^tm1Unc/B2m^tm1Unc H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell
Genetic Background	NOD.Cg-B2m^tm1Unc H2-Ab1^b-tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
B2m^tm1Unc mutation (36 available); any B2m mutation (117 available)
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)
Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell mutation (2 available)

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

cardiovascular system

cardiovascular system phenotype ( J:113267 )

N	• at 22 weeks, no animals show cardiac enlargement or significant mononuclear cell infiltrates

atrioventricular block ( J:113267 )

prolonged PR interval ( J:113267 )

• only animal developed first degree heart block by 24 weeks of age, and no animals develop complete heart block

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell
Genetic Background	NOD.Cg-H2-Ab1^b-tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)
Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell mutation (2 available)

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

mortality/aging

premature death ( J:86540 )

• doubly homozygous mice die between 20 and 60 weeks of age; the female survival curve lags behind the male curve by about 1 week

immune system

immune system phenotype ( J:87013 )

• although CD4⁺ T cells are virtually absent in NOD mice lacking H2-AB1, homozygosity for the transgene restores this cell population in both the spleen and the periphery

• spleen and lymph node cells harvested from homozygous mutant/transgenic NOD mice 2-6 weeks after immunization with human GAD2 (GAD65) in complete Freund's adjuvant exhibit a strong in vitro proliferative response to GAD2

• immunization of homozygous mutant/transgenic NOD mice with human GAD2 (GAD65) in complete Freund's adjuvant produces strong antibody responses versus GAD2

heart inflammation ( J:86540 , J:87013 )

• histologic examination of end-stage hearts reveals pancarditis (J:86540)

• at 5 weeks, doubly homozygous mice exhibit little or no mononuclear-cell cardiac infiltration; the rare positive cases involve only the sites where the great vessels enter/exit the atria (J:86540)

• the mononuclear cells infiltrating hearts of end-stage and of pre-terminal, >20 week old doubly homozygous mice comprise mostly B lymphocytes and plasma cells, with fewer CD4⁺ and CD8⁺ T cells (J:86540)

• older female mice homozygous for both the mutation and the transgene were found to have cardiac immunopathology (J:87013)

salivary gland inflammation ( J:86540 )

• rare, isolated foci of mononuclear cell infiltration may be seen in salivary glands of mice older than 30 weeks

autoimmune response ( J:86540 , J:87013 )

• sera from >25 week old mice with heart block strongly labels both nuclei and cytoplasm of cardiomyocytes by indirect immunofluorescence (J:86540)

• serum from a 6 week old doubly homozygous mouse showed reactivity against mouse and porcine cardiac myosin, and to a lesser extent, skeletal muscle myosin in a western blot assay; serum from an AV-blocked 28 week old mouse gave much stronger signal and detected more bands, suggesting epitope spread over time (J:86540)

• IgG titers measured using purified porcine myosin were significant in doubly homozygous mice at 3 weeks of age (presumably transferred in mothers' milk), dropped to a minimum by 5 weeks and then rose progressively to as high as 1:10⁶ by 20 weeks of age (J:86540)

• porcine cardiac myosin induces in vitro proliferation of splenocytes from doubly mutant mice; this reaction is blocked by an anti-HLA-DQ monoclonal antibody (J:86540)

• irradiation of 5 week old doubly homozygous mice reduces the incidence of AV block at 17 weeks to approximately 25%, when at least 80% of unirradiated mice have AV block (J:86540)

• transfer of splenocytes or splenocytes plus serum from older, AV-blocked mice into irradiated 5 week old mice restores the progression to AV block, whereas serum alone is no more effective than PBS in doing so (J:86540)

• daily injection of doubly homozygous mice from weaning with cyclosporin A significantly delays progression to AV block, although it does not prevent progression to disease in all animals; discontinuation of the drug at 15 weeks leads to rapid disease progression (J:86540)

• a single dose of complete Freund's adjuvant (CFA) administered to 4 week old doubly homozygous NOD mice accelerates progression to AV block, causing complete block in all animals by 12-13 weeks of age (paradoxically, as this treatment delays or prevents onset of autoimmune diabetes in wild-type NOD mice) (J:86540)

• older female mice homozygous for both the mutation and the transgene were found to have cardiac immunopathology (J:87013)

decreased susceptibility to autoimmune disorder ( J:87013 )

• NOD mice homozygous for both the mutation and the transgene do not spontaneously develop diabetes, even by one year of age

• homozygous mutant/transgenic NOD mice fail to develop insulitis

increased autoantibody level ( J:113267 )

• mice produce high titers of autoantibodies against cardiac myosin at 12 weeks of age

myositis ( J:86540 )

• rare, isolated foci of mononuclear cell invasion may be observed in skeletal muscle of mice older than 30 weeks

lung inflammation ( J:86540 )

• by 5 weeks of age, the lungs of doubly homozygous mice have marked lymphocytic infiltration specifically of the ensheathing cardiomyocytes that surround rodents' pulmonary veins, with injury and loss of muscle cells contacted by the invading cells; in older preterminal mice, the pulmonary vessels are completely denuded of ensheathing cardiomyocytes and the mononuclear cell infiltrate has resolved

hematopoietic system

hematopoietic system phenotype ( J:87013 )

N	• although CD4⁺ T cells are virtually absent in NOD mice lacking H2-AB1, homozygosity for the transgene restores this cell population in both the spleen and the periphery

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:87013 )

N	• NOD mice homozygous for both the mutation and the transgene do not spontaneously develop diabetes, even by one year of age • NOD mice homozygous for both the mutation and the transgene are resistant to induction of diabetes by one or two doses of cyclophosphamide

cardiovascular system

abnormal pulmonary vein morphology ( J:86540 )

myocardium necrosis ( J:86540 )

• walls of end-stage atria are infiltrated with mononuclear cells where cardiomyocytes remain, and the cardiomyocytes are dead or dying

• ventricles of terminal mice exhibit scattered aggregates of mononuclear cells associated with injured or dead muscle cells

cardiac fibrosis ( J:86540 )

• end-stage atria are grossly dilated, their walls composed primarily of fibrotic tissue, extremely thin in places and containing few live cardiomyocytes

dilated cardiomyopathy ( J:86540 )

• hearts of doubly homozygous mice are 3-4 times normal size at autopsy; significant enlargement is seen by in vivo echocardiography of pre-terminal mice older than 20 weeks

• high resolution M-mode echocardiography of pre-terminal mice older than 20 weeks reveals significant dilation, with the distance between anterior and posterior endocarial walls greater than twice that of wild-type NOD hearts

decreased heart ventricle muscle contractility ( J:86540 )

• echocardiography of pre-terminal mice older than 20 weeks reveals extremely weak contraction of both ventricles

mitral valve regurgitation ( J:86540 )

• echocardiography of older animals reveals mitral regurgitation

atrioventricular block ( J:86540 )

• serial ECGs showed that at 6 weeks of age, the heart function of doubly homozygous mice is similar to that of NOD controls; by 7 weeks, some mice begin to exhibit first degree atrioventricular (AV) block, which affects increasing numbers of mice and progresses with age such that by 18 weeks, most mice have developed second degree or complete AV block

• some older animals present uncommon ECG profiles, e.g., Wenckeback

prolonged PR interval ( J:113267 )

• nearly all of the mice develop heart block (prolongation of the PR interval) by 24 weeks of age

abnormal heart electrocardiography waveform feature ( J:86540 )

• some older animals present uncommon ECG profiles, e.g., torsade de pointes

heart inflammation ( J:86540 , J:87013 )

• histologic examination of end-stage hearts reveals pancarditis (J:86540)

• older female mice homozygous for both the mutation and the transgene were found to have cardiac immunopathology (J:87013)

muscle

myocardium necrosis ( J:86540 )

• walls of end-stage atria are infiltrated with mononuclear cells where cardiomyocytes remain, and the cardiomyocytes are dead or dying

• ventricles of terminal mice exhibit scattered aggregates of mononuclear cells associated with injured or dead muscle cells

dilated cardiomyopathy ( J:86540 )

• hearts of doubly homozygous mice are 3-4 times normal size at autopsy; significant enlargement is seen by in vivo echocardiography of pre-terminal mice older than 20 weeks

decreased heart ventricle muscle contractility ( J:86540 )

• echocardiography of pre-terminal mice older than 20 weeks reveals extremely weak contraction of both ventricles

myositis ( J:86540 )

• rare, isolated foci of mononuclear cell invasion may be observed in skeletal muscle of mice older than 30 weeks

digestive/alimentary system

salivary gland inflammation ( J:86540 )

• rare, isolated foci of mononuclear cell infiltration may be seen in salivary glands of mice older than 30 weeks

endocrine/exocrine glands

salivary gland inflammation ( J:86540 )

• rare, isolated foci of mononuclear cell infiltration may be seen in salivary glands of mice older than 30 weeks

respiratory system

lung inflammation ( J:86540 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy 1A		DOID:0110425	OMIM:115200	J:86540
myocarditis		DOID:820		J:86540
NOT	type 1 diabetes mellitus	DOID:9744	OMIM:222100	J:87013

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(CD4,HLA-DQA1,HLA-DQB1)N8Ell/Tg(CD4,HLA-DQA1,HLA-DQB1)N8Ell
Genetic Background	NOD.Cg-H2-Ab1^b-tm1Gru Tg(CD4,HLA-DQA1,HLA-DQB1)N8Ell

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)
Tg(CD4,HLA-DQA1,HLA-DQB1)N8Ell mutation (2 available)

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

cardiovascular system

cardiovascular system phenotype ( J:113267 )

N	• no mice develop heart block at any age

immune system

immune system phenotype ( J:113267 )

N	• mice do not develop cardiac autoantibodies, or diabetes at any age

thyroid gland inflammation ( J:113509 )

increased autoantibody level ( J:113509 )

• mice do not develop cardiac myosin autoantibodies, but 100% develop thyroid autoantibodies by 55 weeks of age

endocrine/exocrine glands

enlarged thyroid gland ( J:113509 )

• 25% of mice with thyroiditis develop thyroid gland enlargement and goiter

thyroid gland inflammation ( J:113509 )

homeostasis/metabolism

increased circulating thyroid-stimulating hormone level ( J:113509 )

• a subset of mice with an enlarged thyroid gland develop thyroid failure with elevated serum TSH levels

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)70Myl/0
Genetic Background	NOD.Cg-H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)70Myl

Find Mice

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

cardiovascular system

myocardium necrosis ( J:88055 )

• associated with myocarditis with lymphocytic infiltrates

heart inflammation ( J:88055 )

• hearts show extensive mononuclear infiltrates in the atria; ventricles show focal infiltrates

myocarditis ( J:88055 )

• myocarditis development is transgene- and NOD-specific; the transgenics all exhibit myocarditis

digestive/alimentary system

salivary gland inflammation ( J:88055 )

• observed in transgenic and non-transgenic littermates with equal frequency

endocrine/exocrine glands

salivary gland inflammation ( J:88055 )

• observed in transgenic and non-transgenic littermates with equal frequency

insulitis ( J:88055 )

• transgenic mice show insulitis, but pancreatic beta cell damage is not sufficient to result in clinical diabetes

immune system

heart inflammation ( J:88055 )

• hearts show extensive mononuclear infiltrates in the atria; ventricles show focal infiltrates

myocarditis ( J:88055 )

• myocarditis development is transgene- and NOD-specific; the transgenics all exhibit myocarditis

salivary gland inflammation ( J:88055 )

• observed in transgenic and non-transgenic littermates with equal frequency

insulitis ( J:88055 )

• transgenic mice show insulitis, but pancreatic beta cell damage is not sufficient to result in clinical diabetes

increased autoantibody level ( J:88055 )

• transgenic mice line 73 show the highest prevalence and titers of cardiac tissue autoantibodies (16/18 mice are positive), while only 5/24 line 70 transgenics are positive and have lower antibody titers

muscle

myocardium necrosis ( J:88055 )

• associated with myocarditis with lymphocytic infiltrates

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)73Myl/0
Genetic Background	NOD.Cg-H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)73Myl

Find Mice

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

mortality/aging

premature death ( J:88055 )

• >50% of transgenics (lines 73 and 275) die by 40 weeks of age; line 70 mice do not show significant premature death

homeostasis/metabolism

abnormal atrial thrombosis ( J:88055 )

• massive mural thrombi adjacent to damaged tissue in atria are observed

cyanosis ( J:88055 )

• consistent with congestive heart failure

edema ( J:88055 )

• consistent with congestive heart failure

pleural effusion ( J:88055 )

• upon necropsy, diseased mice show varying degrees of pleural effusions

cardiovascular system

abnormal myocardial fiber morphology ( J:88055 )

• myocyte degeneration and vacuolization are observed in atria, consistent with myocarditis

myocardial fiber degeneration ( J:88055 )

myocardium necrosis ( J:88055 )

• associated with myocarditis with lymphocytic infiltrates

enlarged heart ( J:88055 )

• diseased mice upon death are found to have enlarged hearts with ischemic coloration

• most healthy-appearing mice display marked cardiac enlargement at 40 weeks

abnormal heart ventricle morphology ( J:88055 )

• ventricular inflammatory lesions are composed of large numbers of CD4+ and CD8+ T cells with many F4/80 macrophages and few B cells

liver hemorrhage ( J:88055 )

• enlarged livers show changes characteristic of centrilobular hepatic necrosis and hemorrhage

congestive heart failure ( J:88055 )

• many transgenic mice display symptoms of congestive heart failure; line 70 transgenics do not develop symptoms of congestive heart failure

heart inflammation ( J:88055 )

• hearts show extensive mononuclear infiltrates in the atria; ventricles show focal infiltrates

myocarditis ( J:88055 )

• myocarditis development is transgene- and NOD-specific; the transgenics all exhibit myocarditis

endocrine/exocrine glands

salivary gland inflammation ( J:88055 )

• observed in transgenic and non-transgenic littermates with equal frequency

insulitis ( J:88055 )

• transgenic mice show insulitis, but pancreatic beta cell damage is not sufficient to result in clinical diabetes

immune system

heart inflammation ( J:88055 )

• hearts show extensive mononuclear infiltrates in the atria; ventricles show focal infiltrates

myocarditis ( J:88055 )

• myocarditis development is transgene- and NOD-specific; the transgenics all exhibit myocarditis

salivary gland inflammation ( J:88055 )

• observed in transgenic and non-transgenic littermates with equal frequency

insulitis ( J:88055 )

• transgenic mice show insulitis, but pancreatic beta cell damage is not sufficient to result in clinical diabetes

increased autoantibody level ( J:88055 )

• transgenic mice line 73 show the highest prevalence and titers of cardiac tissue autoantibodies (16/18 mice are positive), while only 5/24 mice of line 70 are positive with lower antibody titers

liver/biliary system

liver hemorrhage ( J:88055 )

• enlarged livers show changes characteristic of centrilobular hepatic necrosis and hemorrhage

abnormal liver morphology ( J:88055 )

• livers show pathological changes characteristic of severe cardiac insufficiency and centrilobular hepatic necrosis and hemorrhage

enlarged liver ( J:88055 )

• upon necropsy, diseased mice show enlargement and darkening of the liver

digestive/alimentary system

salivary gland inflammation ( J:88055 )

• observed in transgenic and non-transgenic littermates with equal frequency

behavior/neurological

lethargy ( J:88055 )

• consistent with congestive heart failure

muscle

abnormal myocardial fiber morphology ( J:88055 )

• myocyte degeneration and vacuolization are observed in atria, consistent with myocarditis

myocardial fiber degeneration ( J:88055 )

myocardium necrosis ( J:88055 )

• associated with myocarditis with lymphocytic infiltrates

respiratory system

pleural effusion ( J:88055 )

• upon necropsy, diseased mice show varying degrees of pleural effusions

abnormal breathing pattern ( J:88055 )

• mice show acute onset of labored breathing

growth/size/body

enlarged heart ( J:88055 )

• diseased mice upon death are found to have enlarged hearts with ischemic coloration

• most healthy-appearing mice display marked cardiac enlargement at 40 weeks

enlarged liver ( J:88055 )

• upon necropsy, diseased mice show enlargement and darkening of the liver

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Ighm^tm1Cgn/Ighm^tm1Cgn Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell
Genetic Background	NOD.Cg-Ighm^tm1Cgn H2-Ab1^b-tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)
Ighm^tm1Cgn mutation (18 available); any Ighm mutation (57 available)
Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell mutation (2 available)

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

cardiovascular system

enlarged heart ( J:113267 )

• magnitude of cardiac enlargement is similar to NOD transgenic H2-Ab1-null, Igh-6-sufficient mice

abnormal PR interval ( J:113267 )

• appearance of heart block is not significantly different from NOD transgenic H2-Ab1-null, Igh-6-sufficient mice

heart inflammation ( J:113267 )

• at 22 weeks, mice show mononuclear cell infiltrates in heart walls

immune system

heart inflammation ( J:113267 )

• at 22 weeks, mice show mononuclear cell infiltrates in heart walls

growth/size/body

enlarged heart ( J:113267 )

• magnitude of cardiac enlargement is similar to NOD transgenic H2-Ab1-null, Igh-6-sufficient mice

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Rag1^tm1Mom/Rag1^tm1Mom Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell/Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell
Genetic Background	NOD.Cg-Rag1^tm1Mom H2-Ab1^b-tm1Gru Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
H2-Ab1^b-tm1Gru mutation (13 available); any H2-Ab1 mutation (78 available)
Rag1^tm1Mom mutation (56 available); any Rag1 mutation (133 available)
Tg(CD2-CD4,HLA-DQA1,HLA-DQB1)1Ell mutation (2 available)

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

cardiovascular system

cardiovascular system phenotype ( J:113267 )

N	• animals have normal sized hearts, normal ECG, and show no sign of autoimmune pathology

enlarged heart ( J:113267 )

• recipient animals develop cardiomegaly by 12 weeks after transfer

prolonged PR interval ( J:113267 )

• mice receiving splenic lymphocytes from animals with heart block display first-degree heart block as early as 2 weeks after transfer, with 50% progressing to complete heart block in 8 weeks

heart inflammation ( J:113267 )

• recipient animals develop mononuclear cell infiltrates within heart wall by 12 weeks after transplant

myocarditis ( J:113267 )

• when young mice receive splenic lymphocytes from older NOD.DQ8/H2Ab-1 mice with heart block, myocarditis is triggered in 100% of recipients

immune system

heart inflammation ( J:113267 )

• recipient animals develop mononuclear cell infiltrates within heart wall by 12 weeks after transplant

myocarditis ( J:113267 )

• when young mice receive splenic lymphocytes from older NOD.DQ8/H2Ab-1 mice with heart block, myocarditis is triggered in 100% of recipients

increased autoantibody level ( J:113267 )

• anticardiac myosin autoantibodies reach a titer of 1:10000 in recipient mice at 12 weeks posttransfer

abnormal response to transplant ( J:113267 )

• younger mice receiving splenic lymphocytes from older DQ8 transgenic, H2-Ab1-null mice with heart block develop heart block, myocarditis, and autoantibodies

• when younger mice receive serum from the same older animals, no cardiac pathology is observed

• recipient mice receiving CD4 T cells from older donor animals with heart block develop heart block as early as 4 weeks posttransfer; all animals are diseased by 12 weeks and upon necropsy, heart are enlarged

• mononuclear cells are more numerous and infiltrates more widespread than in animals that receive total splenocytes (containing CD4 T cells) in the myocardium

• disease onset is somewhat accelerated compared to recipients receiving total lymphocytes;

growth/size/body

enlarged heart ( J:113267 )

• recipient animals develop cardiomegaly by 12 weeks after transfer

Allelic Composition	H2-Ab1^b-tm1Gru/H2-Ab1^b-tm1Gru Rag1^tm1Mom/Rag1^tm1Mom Tg(HLA-DQA1,HLA-DQB1)73Myl/0
Genetic Background	NOD.Cg-Rag1^tm1Mom H2-Ab1^b-tm1Gru Tg(HLA-DQA1,HLA-DQB1)73Myl

Find Mice

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

cardiovascular system

myocarditis ( J:88055 )

• mice do not develop spontaneous myocarditis like NOD.B6-H2Ab1^tm1Gru-Tg(HLA-DQA1,HLA-DQB1)73 mice

immune system

myocarditis ( J:88055 )

• mice do not develop spontaneous myocarditis like NOD.B6-H2Ab1^tm1Gru-Tg(HLA-DQA1,HLA-DQB1)73 mice

abnormal response to transplant ( J:88055 )

• injection of splenocytes from myocarditis-affected donors into healthy transgenic mice results in acute onset of symptoms of severe heart failure 3 weeks post-transfer, reproducing symptoms of the donor mice

• injection of serum from diseased donors with high autoantibody titer does not result in myocarditis

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