Phenotypes associated with this allele

• Allele Symbol: Cd86^tm2Shr
• Allele Name: targeted mutation 2, Arlene H Sharpe
• Allele ID: MGI:2159105
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr	129.SJL-Cd86^tm2Shr	MGI:3620768
cx2	Cd86^tm2Shr/Cd86^tm2Shr Icos^tm1Flv/Icos^tm1Flv	involves: 129S1/Sv * 129S4/SvJaeSor	MGI:3851527
cx3	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr	involves: 129S4/SvJae	MGI:3618330
cx4	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr	involves: 129S4/SvJae * BALB/c	MGI:3662675
cx5	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr Ctla4^tm1Shr/Ctla4^tm1Shr	involves: 129S4/SvJae * BALB/c	MGI:3714352
cx6	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr	involves: 129S4/SvJae * C57BL/6J * SJL	MGI:3620769
cx7	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr Tg(Ighm-Ctla4Ig/Cd80)1Jbs/0	involves: 129S4/SvJae * FVB/N * NOD	MGI:3714277
cx8	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr	involves: 129S4/SvJae * NOD	MGI:3620124

Genotype
MGI:3620768

cx1

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

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

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:3851527

cx2

• Allelic Composition: Cd86^tm2Shr/Cd86^tm2Shr; Icos^tm1Flv/Icos^tm1Flv
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor

immune system

abnormal cytokine level ( J:112600 )

• T cells from mice immunized with keyhole limpet hemocyanin (KLH) in CFA (conjugated Freund's adjuvant) produce no IL-4, IL-17a or interferon gamma in response to KLH restimulation

homeostasis/metabolism

abnormal cytokine level ( J:112600 )

• T cells from mice immunized with keyhole limpet hemocyanin (KLH) in CFA (conjugated Freund's adjuvant) produce no IL-4, IL-17a or interferon gamma in response to KLH restimulation

Genotype
MGI:3618330

cx3

• 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

cx4

• 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

cx5

• 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

cx6

• 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

cx7

• 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

cx8

• 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