Mouse Genome Informatics
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    Cd86tm1Shr/Cd86tm1Shr
NOD.129S4-Cd86tm1Shr
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
behavior/neurological
• forelimb grip strength starts weakening at 6 months of age and is less than half that of controls at 8 months of age
• 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
• 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
• in Cd86-deficient mice, numbers of regulatory T cells (Tregs) ie. CD4+CD25+Cd62Lhi, are reduced slightly in the spleen compared to control NOD mice
• T cells proliferate in response to the auto-antigen myelin protein zero
• 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
• at 6 months of age, there is a 1.5 fold increase in the number of CD4+ T cells secreting IFN-gamma
• no female or male mutants on the NOD background developed diabetes compared to 70% and 30% respectively in wild-type Cd86 NOD mice
• 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
• 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
• nulls display severe inflammation in the peripheral nervous system
• some sciatic nerve fibers display increased numbers of Nodes of Ranvier with irregular spacing and irregular myelin sheet thickness
• mice show mononuclear, cellular infiltrate composed of dendritic cells and scattered CD4+ and CD8+ cells
• mice show mononuclear infiltrate in this structure
• mice show mononuclear infiltrate in this structure
• sciatic nerves show electrophysiological indications of a predominantly demyelinating neuropathy
• a dipersion of compound muscle action potentials is observed
• 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)
• sciatic nerve conduction studies reveal a significant difference in conduction velocity

muscle
• 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
• in Cd86-deficient mice, numbers of regulatory T cells (Tregs) ie. CD4+CD25+Cd62Lhi, are reduced slightly in the spleen compared to control NOD mice
• T cells proliferate in response to the auto-antigen myelin protein zero
• 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
OMIM IDRef(s)
Guillain-Barre Syndrome, Familial; GBS 139393 J:71352 , J:142046