Phenotypes associated with this allele

• Allele Symbol: Cd86^tm1Shr
• Allele Name: targeted mutation 1, Arlene H Sharpe
• Allele ID: MGI:1861805
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cd86^tm1Shr/Cd86^tm1Shr	B6.129S4-Cd86^tm1Shr	MGI:5085306
hm2	Cd86^tm1Shr/Cd86^tm1Shr	involves: 129S4/SvJae	MGI:3618329
hm3	Cd86^tm1Shr/Cd86^tm1Shr	NOD.129S4-Cd86^tm1Shr	MGI:3618096
cx4	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm1Shr/Cd86^tm1Shr	B6.129S4-Cd80^tm1Shr Cd86^tm1Shr	MGI:5085302
cx5	Cd86^tm1Shr/Cd86^tm1Shr Marchf1^tm1.1Sish/Marchf1^tm1.1Sish	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:4436871

Genotype
MGI:5085306

hm1

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

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

hematopoietic system

decreased T cell proliferation ( J:57613 )

• T cells primed to myelin oligodendrocyte glycoprotein (MOG) 355-55 peptide exhibit modestly reduced proliferative responses as compared to than controls

immune system

decreased T cell proliferation ( J:57613 )

• T cells primed to myelin oligodendrocyte glycoprotein (MOG) 355-55 peptide exhibit modestly reduced proliferative responses as compared to than controls

increased interferon-gamma secretion ( J:57613 )

• lymph node cells from mice immunized with myelin oligodendrocyte glycoprotein (MOG) 355-55 peptide produce more interferon gamma than wild type cells

cellular

decreased T cell proliferation ( J:57613 )

• T cells primed to myelin oligodendrocyte glycoprotein (MOG) 355-55 peptide exhibit modestly reduced proliferative responses as compared to than controls

Genotype
MGI:3618329

hm2

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

immune system

absent spleen germinal center ( J:39089 )

• there is an absence of germinal center formation in mutants

abnormal humoral immune response ( J:39089 )

• when immunized with trinitrophenyl conjugates of keyhole limpet hemocyanin or ovalbumin, mice produce reduced levels of antibodies compared to wild-type

decreased IgG level ( J:39089 )

• mice produce less than 5% of wild-type levels of IgG1 and IgG2a when immunized with keyhole limpet hemocyanin or ovalbumin conjugates

hematopoietic system

absent spleen germinal center ( J:39089 )

• there is an absence of germinal center formation in mutants

decreased IgG level ( J:39089 )

• mice produce less than 5% of wild-type levels of IgG1 and IgG2a when immunized with keyhole limpet hemocyanin or ovalbumin conjugates

Genotype
MGI:3618096

hm3

• Allelic Composition: Cd86^tm1Shr/Cd86^tm1Shr
• Genetic Background: NOD.129S4-Cd86^tm1Shr

behavior/neurological

decreased grip strength ( J:142046 )

• forelimb grip strength starts weakening at 6 months of age and is less than half that of controls at 8 months of age

hindlimb paralysis ( J:71352 )

• Background Sensitivity: by 20 weeks of age mice start to display a symmetrical mild hind leg paralysis that progresses to a generalized limb paralysis; by 32 weeks of age all female and 30% of male mutant mice display this with the majority of affected mice showing difficulty in walking; this phenotype is not seen when Cd86 nulls are crossed to C57BL/6 or 129/Sv nonautoimmune backgrounds

paresis ( J:142046 )

• severe parapesis occurs to all mice by 28 weeks of age

• sciatic nerve conduction studies reveal a significant difference in distal latency, conduction velocity and amplitude of the motor response

immune system

abnormal T cell proliferation ( J:142046 )

• T cells proliferate in response to the auto-antigen myelin protein zero

decreased T cell proliferation ( J:93421 )

• transplanted diabetogenic T cells from Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi mice divided primarily in the pancreatic lymph nodes of NOD mice whereas, transferred T cells show reduced proliferation in Cd86-deficient NOD mice

• depletion of Tregs in Cd86-deficient mice partially restores proliferation of Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi T cells in pancreatic lymph nodes

decreased regulatory T cell number ( J:93421 )

• in Cd86-deficient mice, numbers of regulatory T cells (Tregs) ie. CD4+CD25+Cd62L^hi, are reduced slightly in the spleen compared to control NOD mice

increased interferon-gamma secretion ( J:142046 )

• at 6 months of age, there is a 1.5 fold increase in the number of CD4⁺ T cells secreting IFN-gamma

decreased susceptibility to autoimmune diabetes ( J:71352 )

• no female or male mutants on the NOD background developed diabetes compared to 70% and 30% respectively in wild-type Cd86 NOD mice

increased susceptibility to autoimmune diabetes ( J:93421 )

• when CD80 expression is blocked, 2-4-week old mice become diabetic, with 90% developing diabetes by 18 weeks; untreated mice are protected from diabetes

increased autoantibody level ( J:142046 )

• auto-antibodies to myelin protein zero are detected in sera of mice starting at 2-4 months of age

• by 8 months of age, all mice have detectable antibodies to this protein

• the isotype frequency are IgG3 > IgG1 > IgG2c > IgG2b

nervous system

abnormal nervous system morphology ( J:71352 )

• nulls display severe inflammation in the peripheral nervous system

abnormal myelin sheath morphology ( J:71352 )

• some sciatic nerve fibers display increased numbers of Nodes of Ranvier with irregular spacing and irregular myelin sheet thickness

abnormal dorsal root ganglion morphology ( J:71352 )

• mice show mononuclear, cellular infiltrate composed of dendritic cells and scattered CD4+ and CD8+ cells

abnormal dorsal spinal root morphology ( J:71352 )

• mice show mononuclear infiltrate in this structure

abnormal ventral spinal root morphology ( J:71352 )

• mice show mononuclear infiltrate in this structure

demyelination ( J:71352 )

• sciatic nerves show electrophysiological indications of a predominantly demyelinating neuropathy

abnormal action potential ( J:71352 )

• a dipersion of compound muscle action potentials is observed

abnormal nerve conduction ( J:71352 , J:142046 )

• in the sciatic nerve, prolongation of distal latencies and a slowing of conduction velocity is seen with respect to wild-type NOD mice, with conduction block observed in severe cases (J:71352)

• sciatic nerve conduction studies reveal a significant difference in distal latency, conduction velocity and amplitude of the motor response (J:142046)

decreased nerve conduction velocity ( J:142046 )

• sciatic nerve conduction studies reveal a significant difference in conduction velocity

muscle

muscular atrophy ( J:71352 )

• skeletal muscles show severe focal neurogenic atrophy in severely affected animals, but there are no detectable lesions in the brain or spinal cord

hematopoietic system

abnormal T cell proliferation ( J:142046 )

• T cells proliferate in response to the auto-antigen myelin protein zero

decreased T cell proliferation ( J:93421 )

• transplanted diabetogenic T cells from Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi mice divided primarily in the pancreatic lymph nodes of NOD mice whereas, transferred T cells show reduced proliferation in Cd86-deficient NOD mice

• depletion of Tregs in Cd86-deficient mice partially restores proliferation of Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi T cells in pancreatic lymph nodes

decreased regulatory T cell number ( J:93421 )

• in Cd86-deficient mice, numbers of regulatory T cells (Tregs) ie. CD4+CD25+Cd62L^hi, are reduced slightly in the spleen compared to control NOD mice

cellular

abnormal T cell proliferation ( J:142046 )

• T cells proliferate in response to the auto-antigen myelin protein zero

decreased T cell proliferation ( J:93421 )

• transplanted diabetogenic T cells from Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi mice divided primarily in the pancreatic lymph nodes of NOD mice whereas, transferred T cells show reduced proliferation in Cd86-deficient NOD mice

• depletion of Tregs in Cd86-deficient mice partially restores proliferation of Tg(TcraBDC2.5)1Doi Tg(TcrbBDC2.5)2Doi T cells in pancreatic lymph nodes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Guillain-Barre syndrome		DOID:12842	OMIM:139393	J:71352 , J:142046

Genotype
MGI:5085302

cx4

• 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:4436871

cx5

• Allelic Composition: Cd86^tm1Shr/Cd86^tm1Shr; Marchf1^tm1.1Sish/Marchf1^tm1.1Sish
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

immune system

decreased interleukin-12 secretion ( J:157516 )

• in dendritic cells following LPS or anti-CD40 antibody stimulation

decreased tumor necrosis factor secretion ( J:157516 )

• in dendritic cells following LPS or anti-CD40 antibody stimulation