Phenotypes associated with this allele

• Allele Symbol: Tg(CD2-Ifngr2)2Pbro
• Allele Name: transgene insertion 2, Paul B Rothman
• Allele ID: MGI:3785869
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
tg1	Tg(CD2-Ifngr2)2Pbro/?	B6.Cg-Tg(CD2-Ifngr2)2Pbro	MGI:3785870
tg2	Tg(CD2-Ifngr2)2Pbro/?	NOD.Cg-Tg(CD2-Ifngr2)2Pbro	MGI:3789004

Genotype
MGI:3785870

tg1

• Allelic Composition: Tg(CD2-Ifngr2)2Pbro/?
• Genetic Background: B6.Cg-Tg(CD2-Ifngr2)2Pbro

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

immune system

immune system phenotype ( J:134448 )

N • flow cytometric analysis of thymocytes, splenocytes, and bone marrow cells indicates normal lymphocyte population distributions

abnormal T-helper 1 cell differentiation ( J:134448 )

• diminished interferon gamma production by stimulated splenocytes differentiated in vitro with Th1 polarizing cytokines

abnormal T-helper 1 physiology ( J:134448 )

• Ifngr2 is expressed from the transgene and the endogenous gene in DNP-KLH induced TH1 and TH2 clones and treatment with interferon gamma activates Stat1

• Th1 cells differentiated in vitro have a greater proliferative response to anti-CD3 in the presence of IL2

• CD4<+> splenocytes from KLH-immunized mice do not produce interferon gamma but do proliferate normally in response to antigen-specific stimulation, yet antigen-specific IgG2a are not detected after immunization and the second booster with KLH, although IgG2a and IgG1 production are normal from purified B cells stimulated with LPS and interferon gamma or interleukin 4

• increased susceptibility to Leishmania major

increased susceptibility to parasitic infection ( J:134448 )

hematopoietic system

abnormal T-helper 1 cell differentiation ( J:134448 )

• diminished interferon gamma production by stimulated splenocytes differentiated in vitro with Th1 polarizing cytokines

abnormal T-helper 1 physiology ( J:134448 )

• Ifngr2 is expressed from the transgene and the endogenous gene in DNP-KLH induced TH1 and TH2 clones and treatment with interferon gamma activates Stat1

• Th1 cells differentiated in vitro have a greater proliferative response to anti-CD3 in the presence of IL2

• CD4<+> splenocytes from KLH-immunized mice do not produce interferon gamma but do proliferate normally in response to antigen-specific stimulation, yet antigen-specific IgG2a are not detected after immunization and the second booster with KLH, although IgG2a and IgG1 production are normal from purified B cells stimulated with LPS and interferon gamma or interleukin 4

• increased susceptibility to Leishmania major

Genotype
MGI:3789004

tg2

• Allelic Composition: Tg(CD2-Ifngr2)2Pbro/?
• Genetic Background: NOD.Cg-Tg(CD2-Ifngr2)2Pbro

immune system

immune system phenotype ( J:81981 )

N • brain, liver, kidney, lung, and large intestines show no obvious leukocyte infiltration

insulitis ( J:81981 )

• the mean insulitis scores of 9 week old females is the same in transgenic and non-transgenic NOD controls and three females surviving to 8 to 12 weeks of age developed overt type 1 diabetes

ovary inflammation ( J:81981 )

♀ • occasionally found

abnormal splenic cell ratio ( J:81981 )

• Background Sensitivity: approximately 3 fold and 2 fold reduction in the proportion of splenic CD4<+> and CD8<+> T cells respectively and increased proportions of splenic B cells, splenic macrophages and dendritic cells, and splenic granulocytes

abnormal T-helper 1 physiology ( J:81981 )

decreased interferon-gamma secretion ( J:81981 )

• CD4 T cells activated under Th1 priming conditions produce 10 fold less interferon gamma than controls upon secondary anti-CD3 stimulation

• splenic T cells stimulated with anti-CD3 produce very little interferon gamma upon secondary stimulation relative to NOD controls

decreased interleukin-4 secretion ( J:81981 )

• Background Sensitivity: On the NOD background, but not the C57BL/6 background, CD4 T cells activated under Th2 priming conditions product 10 fold less IL4 than controls upon secondary anti-CD3 restimulation

• splenic T cells stimulated with anti-CD3 produce very little IL4 upon secondary stimulation relative to NOD controls

decreased tumor necrosis factor secretion ( J:81981 )

• CD4 T cells activated under Th1 priming conditions produce less TNF alpha than controls upon secondary anti-CD3 stimulation

• splenic T cells stimulated with anti-CD3 produce very little tumor necrosis factor alpha upon secondary stimulation relative to NOD controls

myositis ( J:81981 )

• Background Sensitivity: a CD8<+> T cell dependent lethal paralytic syndrome develops before 10 weeks of age associated with a massive leukocytic inflammatory response initiating exterior to the lumbar reion of the spinal column and progressing toward the cervical region and into the peripheral limbs. Destruction of muscle, but not peripheral nerve tissue, is seen

• Background Sensitivity: this paraspinal myositis develops in all transgene carriers but with faster kinetics in females than in males

• Background Sensitivity: infiltration of macrophages, CD8<+> T cells and a small number of CD4<+> T cells, but not B cells or granulocytes are found in the myositis lesions; depletion of CD8<+> T cells via injection of anti-CD8 antibodies can prevent disease onset, whereas injection with anti-CD4 antibodies only slightly delays onset

• Background Sensitivity: splenocytes from paralytic carriers transfer the disease to NOD-Prkdc^scid hosts proving autoimmune-mediated myositis

muscle

myositis ( J:81981 )

• Background Sensitivity: a CD8<+> T cell dependent lethal paralytic syndrome develops before 10 weeks of age associated with a massive leukocytic inflammatory response initiating exterior to the lumbar reion of the spinal column and progressing toward the cervical region and into the peripheral limbs. Destruction of muscle, but not peripheral nerve tissue, is seen

• Background Sensitivity: this paraspinal myositis develops in all transgene carriers but with faster kinetics in females than in males

• Background Sensitivity: infiltration of macrophages, CD8<+> T cells and a small number of CD4<+> T cells, but not B cells or granulocytes are found in the myositis lesions; depletion of CD8<+> T cells via injection of anti-CD8 antibodies can prevent disease onset, whereas injection with anti-CD4 antibodies only slightly delays onset

• Background Sensitivity: splenocytes from paralytic carriers transfer the disease to NOD-Prkdc^scid hosts proving autoimmune-mediated myositis

hematopoietic system

abnormal splenic cell ratio ( J:81981 )

• Background Sensitivity: approximately 3 fold and 2 fold reduction in the proportion of splenic CD4<+> and CD8<+> T cells respectively and increased proportions of splenic B cells, splenic macrophages and dendritic cells, and splenic granulocytes

abnormal T-helper 1 physiology ( J:81981 )

endocrine/exocrine glands

insulitis ( J:81981 )

• the mean insulitis scores of 9 week old females is the same in transgenic and non-transgenic NOD controls and three females surviving to 8 to 12 weeks of age developed overt type 1 diabetes

ovary inflammation ( J:81981 )

♀ • occasionally found

reproductive system

ovary inflammation ( J:81981 )

♀ • occasionally found

growth/size/body

weight loss ( J:81981 )

• Background Sensitivity: associated with the onset of paralytic myositis