Phenotypes associated with this allele

• Allele Symbol: Cd80^tm1Shr
• Allele Name: targeted mutation 1, Arlene H Sharpe
• Allele ID: MGI:1861804
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cd80^tm1Shr/Cd80^tm1Shr	involves: 129S4/SvJae	MGI:2662258
cx2	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr	129.SJL-Cd86^tm2Shr	MGI:3620768
cx3	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm1Shr/Cd86^tm1Shr	B6.129S4-Cd80^tm1Shr Cd86^tm1Shr	MGI:5085302
cx4	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr	involves: 129S4/SvJae	MGI:3618330
cx5	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr	involves: 129S4/SvJae * BALB/c	MGI:3662675
cx6	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr Ctla4^tm1Shr/Ctla4^tm1Shr	involves: 129S4/SvJae * BALB/c	MGI:3714352
cx7	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr	involves: 129S4/SvJae * C57BL/6J * SJL	MGI:3620769
cx8	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr Tg(Ighm-Ctla4Ig/Cd80)1Jbs/0	involves: 129S4/SvJae * FVB/N * NOD	MGI:3714277
cx9	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr	involves: 129S4/SvJae * NOD	MGI:3620124

Genotype
MGI:2662258

hm1

• Allelic Composition: Cd80^tm1Shr/Cd80^tm1Shr
• Genetic Background: involves: 129S4/SvJae

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

immune system

decreased B cell proliferation ( J:74662 )

• B cells stimulated with LPS and dextran show a mixed lymphocyte response that is reduced by 70% compared to wild-type

abnormal immunoglobulin level ( J:39089 )

• production of IgG1, IgG2a and IgM is reduced to 25-50% of wild-type after immunization with trinitrophenyl conjugates of keyhole limpet hemocyanin or ovalbumin

hematopoietic system

decreased B cell proliferation ( J:74662 )

• B cells stimulated with LPS and dextran show a mixed lymphocyte response that is reduced by 70% compared to wild-type

abnormal immunoglobulin level ( J:39089 )

• production of IgG1, IgG2a and IgM is reduced to 25-50% of wild-type after immunization with trinitrophenyl conjugates of keyhole limpet hemocyanin or ovalbumin

cellular

decreased B cell proliferation ( J:74662 )

• B cells stimulated with LPS and dextran show a mixed lymphocyte response that is reduced by 70% compared to wild-type

Genotype
MGI:3620768

cx2

• Allelic Composition: Cd80^tm1Shr/Cd80^tm1Shr; Cd86^tm2Shr/Cd86^tm2Shr
• Genetic Background: 129.SJL-Cd86^tm2Shr

cellular

decreased cell proliferation ( J:78992 )

• proliferative responses of lymph node cells to myelin proteolipid protein peptide 139-151 or 178-191 are impaired in null mice compared to wild-type

immune system

decreased interleukin-2 secretion ( J:78992 )

• no IL-2 production could be detected in draining lymph node cells

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:78992 )

• mice develop EAE, but severity is lower and time of onset is delayed compared to wild-type SJL mice

increased susceptibility to experimental autoimmune encephalomyelitis ( J:78992 )

• Background Sensitivity: null mice on a 129 background are susceptible to EAE, whereas nulls on a B6 background are resistant

nervous system

abnormal meninges morphology ( J:78992 )

• in mice exhibiting EAE, there are lesions in the meniges and parenchyma of the spinal cord and brain; number of lesions is lower than in wild-type mice with EAE

• lesions associated with white matter vacuolation occur with higher incidence in null mice compared to wild-type mice with EAE

Genotype
MGI:5085302

cx3

• Allelic Composition: Cd80^tm1Shr/Cd80^tm1Shr; Cd86^tm1Shr/Cd86^tm1Shr
• Genetic Background: B6.129S4-Cd80^tm1Shr Cd86^tm1Shr

hematopoietic system

decreased T cell proliferation ( J:57613 )

• T cells primed by MOG 355-55 peptide exhibit markedly impaired proliferative responses as compared to controls

immune system

decreased T cell proliferation ( J:57613 )

• T cells primed by MOG 355-55 peptide exhibit markedly impaired proliferative responses as compared to controls

increased interferon-gamma secretion ( J:57613 )

• lymph node cells from mice immunized with MOG 355-55 peptide produce a greater than 30 fold increase in interferon gamma as compared to wild type cells

increased tumor necrosis factor secretion ( J:57613 )

• lymph node cells from mice immunized with MOG 355-55 peptide produce increased amounts of TNFalpha as compared to wild type cells, although the increase is limited to the first 24 hours of culture

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:57613 )

• mice do not develop clinical symptoms of EAE following stimulation by myelin oligodendrocyte glycoprotein (MOG) 355-55 peptide or by adoptive transfer

brain inflammation ( J:57613 )

• 50% of mice exhibit inflammatory lesions in meninges and CNS parenchyma as compared to 80% in wild-type following 35 day observation period after EAE induction

• inflammatory foci are limited to leptomeninges

nervous system

brain inflammation ( J:57613 )

• 50% of mice exhibit inflammatory lesions in meninges and CNS parenchyma as compared to 80% in wild-type following 35 day observation period after EAE induction

• inflammatory foci are limited to leptomeninges

cellular

decreased T cell proliferation ( J:57613 )

• T cells primed by MOG 355-55 peptide exhibit markedly impaired proliferative responses as compared to controls

Genotype
MGI:3618330

cx4

• Allelic Composition: Cd80^tm1Shr/Cd80^tm1Shr; Cd86^tm2Shr/Cd86^tm2Shr
• Genetic Background: involves: 129S4/SvJae

immune system

decreased regulatory T cell number ( J:113109 , J:205441 )

• mice have 0.3% CD4+CD25^hiCD62L+ regulatory T cells compared to 4% in NOD controls (J:113109)

• in the thymus (J:205441)

abnormal spleen morphology ( J:39089 )

• after immunization with complete Freund's adjuvant, spleens examined 7-10 days later were significantly smaller than wild-type

increased IgG3 level ( J:39089 )

• mutants have a 3 to 5-fold elevation in IgG3

decreased IgG level ( J:39089 )

• unimmunized mice show a 2 to 5-fold reduction in total serum IgG and IgG2a and a 5 to 10-fold reduction in IgG1

decreased IgG1 level ( J:39089 )

decreased IgG2a level ( J:39089 )

increased IgM level ( J:39089 )

• mutants have a 3 to 5-fold elevation in IgM

abnormal T cell physiology ( J:57090 )

• cells secrete more interferon gamma and less Il-4 than Ctla4-null cells

abnormal T cell proliferation ( J:57090 )

• during primary response after antigen stimulation, T cells produce less than cells that are additionally Ctla4-null

abnormal lymph node B cell domain morphology ( J:39089 )

• lymphoid follicles are small, resembling primary follicles without recognizable germinal centers

increased susceptibility to autoimmune diabetes ( J:113109 )

• 100% of mice develop diabetes by 17 weeks

hematopoietic system

decreased regulatory T cell number ( J:113109 , J:205441 )

• mice have 0.3% CD4+CD25^hiCD62L+ regulatory T cells compared to 4% in NOD controls (J:113109)

• in the thymus (J:205441)

abnormal spleen morphology ( J:39089 )

• after immunization with complete Freund's adjuvant, spleens examined 7-10 days later were significantly smaller than wild-type

increased IgG3 level ( J:39089 )

• mutants have a 3 to 5-fold elevation in IgG3

decreased IgG level ( J:39089 )

• unimmunized mice show a 2 to 5-fold reduction in total serum IgG and IgG2a and a 5 to 10-fold reduction in IgG1

decreased IgG1 level ( J:39089 )

decreased IgG2a level ( J:39089 )

increased IgM level ( J:39089 )

• mutants have a 3 to 5-fold elevation in IgM

abnormal T cell physiology ( J:57090 )

• cells secrete more interferon gamma and less Il-4 than Ctla4-null cells

abnormal T cell proliferation ( J:57090 )

• during primary response after antigen stimulation, T cells produce less than cells that are additionally Ctla4-null

cellular

abnormal T cell proliferation ( J:57090 )

• during primary response after antigen stimulation, T cells produce less than cells that are additionally Ctla4-null

Genotype
MGI:3662675

cx5

• Allelic Composition: Cd80^tm1Shr/Cd80^tm1Shr; Cd86^tm2Shr/Cd86^tm2Shr
• Genetic Background: involves: 129S4/SvJae * BALB/c

hematopoietic system

abnormal T cell number ( J:112266 )

• mice have increased CD4/CD8 ratios in the spleen (4.1 vs 2.2 in controls) and in lymph nodes (6.6 vs 2.8 in controls), reciprocal to the decreased ratios seen in transgenic Cd86 or Cd80 mice

decreased double-positive T cell number ( J:112266 )

• ther are fewer double positive cells (74.3%) compared to controls (83.8%) and higher CD4+ cell numbers (17.2% vs 10.5%)

immune system

abnormal T cell number ( J:112266 )

• mice have increased CD4/CD8 ratios in the spleen (4.1 vs 2.2 in controls) and in lymph nodes (6.6 vs 2.8 in controls), reciprocal to the decreased ratios seen in transgenic Cd86 or Cd80 mice

decreased double-positive T cell number ( J:112266 )

• ther are fewer double positive cells (74.3%) compared to controls (83.8%) and higher CD4+ cell numbers (17.2% vs 10.5%)

Genotype
MGI:3714352

cx6

• Allelic Composition: Cd80^tm1Shr/Cd80^tm1Shr; Cd86^tm2Shr/Cd86^tm2Shr; Ctla4^tm1Shr/Ctla4^tm1Shr
• Genetic Background: involves: 129S4/SvJae * BALB/c

immune system

abnormal T cell physiology ( J:57090 )

• T cells differentiate into Th2 cells upon anti-CD3 stimulus

increased T cell proliferation ( J:57090 )

• during secondary stimulation with anti-CD3 and antigen-presenting cells, CD4+ T cells proliferate more than Ctla4-sufficient, CD80/86 null cells

abnormal cytokine secretion ( J:57090 )

• cells produce Il-4 even during primary stimulation with anti-CD3 and APCs, whereas Ctla4-sufficient mice do not, and on secondary stimulation, cells produce more Il-4 and less interferon gamma than Ctla4-sufficient cells

• upon anti-CD28 stimulation in vivo, cells produce Il-4 but wild-type cells do not; mice show less interferon gamma production after anti-CD28 treatment than wild-type mice

hematopoietic system

abnormal T cell physiology ( J:57090 )

• T cells differentiate into Th2 cells upon anti-CD3 stimulus

increased T cell proliferation ( J:57090 )

• during secondary stimulation with anti-CD3 and antigen-presenting cells, CD4+ T cells proliferate more than Ctla4-sufficient, CD80/86 null cells

cellular

increased T cell proliferation ( J:57090 )

• during secondary stimulation with anti-CD3 and antigen-presenting cells, CD4+ T cells proliferate more than Ctla4-sufficient, CD80/86 null cells

Genotype
MGI:3620769

cx7

• Allelic Composition: Cd80^tm1Shr/Cd80^tm1Shr; Cd86^tm2Shr/Cd86^tm2Shr
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * SJL

cellular

decreased cell proliferation ( J:78992 )

• lymph node cells from null animals proliferate poorly compared to wild-type, but do produce IFNG in response to PLP or MOG peptides

immune system

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:78992 )

• null mice on the mixed background are resistant to EAE when immunized with either PLP 139-151 or myelin oligodendrocyte glycoprotein 35-55 compared with wild-type (B6 x SJL)F1 mice

nervous system

abnormal spinal cord meninges morphology ( J:78992 )

• numbers of foci in the meninges and parenchyma of the spinal cords of null mice are lower compared to control mice

Genotype
MGI:3714277

cx8

• Allelic Composition: Cd80^tm1Shr/Cd80^tm1Shr; Cd86^tm2Shr/Cd86^tm2Shr; Tg(Ighm-Ctla4Ig/Cd80)1Jbs/0
• Genetic Background: involves: 129S4/SvJae * FVB/N * NOD

immune system

insulitis ( J:113109 )

• mice show less insulitis compared to non-transgenic double nulls

decreased regulatory T cell number ( J:113109 )

• mice have 0.3% CD4+CD25^hiCD62L+ regulatory T cells compared to 4% in NOD controls

decreased susceptibility to autoimmune diabetes ( J:113109 )

• mice show 40% suppression of diabetes development compared to non-transgenic double null animals

hematopoietic system

decreased regulatory T cell number ( J:113109 )

• mice have 0.3% CD4+CD25^hiCD62L+ regulatory T cells compared to 4% in NOD controls

endocrine/exocrine glands

insulitis ( J:113109 )

• mice show less insulitis compared to non-transgenic double nulls

Genotype
MGI:3620124

cx9

• Allelic Composition: Cd80^tm1Shr/Cd80^tm1Shr; Cd86^tm2Shr/Cd86^tm2Shr
• Genetic Background: involves: 129S4/SvJae * NOD

immune system

insulitis ( J:61905 )

• at 9 weeks, all islets isolated from male and female homozygous mice showed high infiltration, whereas in wild-type NOD mice, only 10% and 3% of islets obtained from female and male mice displayed severe insulitis; no insulitis is detected at 4 weeks and at 6 weeks most islets aren't infiltrated

abnormal CD4-positive, alpha-beta T cell physiology ( J:61905 )

• there is a profound decrease in numbers of CD4+CD25+ T cells in homozygotes compared to wild-type with levels lower than in CD28-null mice on a NOD background

abnormal cytokine secretion ( J:61905 )

• in T cells and supernatants collected after stimulation with antil-CD3, production of all cytokines is reduced compared to wild-type levels

increased susceptibility to autoimmune diabetes ( J:61905 )

• almost 100% of homozygous mice become diabetic (blood glucose >300 mg/dl on 2 consecutive measurements) by 18 weeks of age, compared to 70% of female and 20% of male wild-type NOD controls or 40% of female and 10% of male wild-type mice

endocrine/exocrine glands

insulitis ( J:61905 )

• at 9 weeks, all islets isolated from male and female homozygous mice showed high infiltration, whereas in wild-type NOD mice, only 10% and 3% of islets obtained from female and male mice displayed severe insulitis; no insulitis is detected at 4 weeks and at 6 weeks most islets aren't infiltrated

hematopoietic system

abnormal CD4-positive, alpha-beta T cell physiology ( J:61905 )

• there is a profound decrease in numbers of CD4+CD25+ T cells in homozygotes compared to wild-type with levels lower than in CD28-null mice on a NOD background

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:61905