Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptpn22tm2Achn mutation
(1 available);
any
Ptpn22 mutation
(36 available)
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immune system
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• double-positive thymocytes have CD5 and CD69 slighlty upregulated and are more responsive to in vitro stimulation
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• the CD4:CD8 T cell ratio in the periphery is over 1.5 at six months of age
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• CD44hi CD62Llo memory T cells are increased about 2-fold at 6 months of age compared to controls
• differences are noticeable at 3 months of age with increases progressing with age
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• the activation marker CD69 is slightly upregulated on both CD4 and CD8 T cells in vivo
• nave CD8 T cells are hyper-response to in vitro stimulation
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• double-positive thymocytes are more responsive to in vitro stimulation than controls
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• mild lymphadenopathy is observed in these mice
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hematopoietic system
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• double-positive thymocytes have CD5 and CD69 slighlty upregulated and are more responsive to in vitro stimulation
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• the CD4:CD8 T cell ratio in the periphery is over 1.5 at six months of age
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• CD44hi CD62Llo memory T cells are increased about 2-fold at 6 months of age compared to controls
• differences are noticeable at 3 months of age with increases progressing with age
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• the activation marker CD69 is slightly upregulated on both CD4 and CD8 T cells in vivo
• nave CD8 T cells are hyper-response to in vitro stimulation
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• double-positive thymocytes are more responsive to in vitro stimulation than controls
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endocrine/exocrine glands
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• double-positive thymocytes are more responsive to in vitro stimulation than controls
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptpn22tm2Achn mutation
(1 available);
any
Ptpn22 mutation
(36 available)
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growth/size/body
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• homozygous mice older than 6 months develop enlarged spleens
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hematopoietic system
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• homozygous mice older than 6 months develop enlarged spleens
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• associated with the increased germinal center formation is an increase in GL-7+ B cells and CD23+ follicular B cells
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• an increase in CD23+ follicular B cells is seen
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• homozygous mice display increased numbers of large, well-formed germinal centers compared to wild-type mice
• no evidence of autoimmune-mediated organ damage is seen despite the spontaneous formation off germinal centers
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• serum levels of IgE are increased in homozygotes compared to wild-type mice
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• associated with the increased germinal center formation is an increase IgG1+ foci
• serum levels of IgG1 are increased in homozygotes compared to wild-type mice
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• serum levels of IgG2a are increased in homozygotes compared to wild-type mice
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• following antigen stimulation increased development of CD4+ and CD8+ T cells is seen in homozygotes
• 3 - 4 days after T cell receptor activation CD4+ and CD8+ T cells display increased cell cycling, enhanced proliferation, and increased cytokine production compared to T cells from wild-type mice
• negative selection of T cells is unaffected in homozygous mice
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immune system
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• homozygous mice older than 6 months develop enlarged spleens
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• associated with the increased germinal center formation is an increase in GL-7+ B cells and CD23+ follicular B cells
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• an increase in CD23+ follicular B cells is seen
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• homozygous mice display increased numbers of large, well-formed germinal centers compared to wild-type mice
• no evidence of autoimmune-mediated organ damage is seen despite the spontaneous formation off germinal centers
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• serum levels of IgE are increased in homozygotes compared to wild-type mice
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• associated with the increased germinal center formation is an increase IgG1+ foci
• serum levels of IgG1 are increased in homozygotes compared to wild-type mice
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• serum levels of IgG2a are increased in homozygotes compared to wild-type mice
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• following antigen stimulation increased development of CD4+ and CD8+ T cells is seen in homozygotes
• 3 - 4 days after T cell receptor activation CD4+ and CD8+ T cells display increased cell cycling, enhanced proliferation, and increased cytokine production compared to T cells from wild-type mice
• negative selection of T cells is unaffected in homozygous mice
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• homozygous mice display increased numbers of large, well-formed germinal centers compared to wild-type mice
• no evidence of autoimmune-mediated organ damage is seen despite the spontaneous formation off germinal centers
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• homozygous mice older than 6 months develop enlarged lymph nodes
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mortality/aging
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• 33% of mice die between 10 and 12 months of age
• likely cause of death is glomerulonephritis
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growth/size/body
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• decreased body weight is observed in mice starting at 6 months of age
• mice that survive to 12 months of age are smaller than controls
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immune system
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• double-positive thymocytes have CD5 and CD69 upregulated and are hyper-responsive to in vitro stimulation
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• T1 and T2 B cell numbers are increased in the spleen similar to mice homozygous for just the Ptprctm1Weis allele
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• follicular B cell numbers are reduced by about a third compared to controls
• a similar phenotype is observed in mice homozygous for just the Ptprctm1Weis allele
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• plasma cell numbers in the spleen is increased 4-fold at 3 months of age compared to controls
• a similar phenotype is observed in mice homozygous for just the Ptprctm1Weis allele
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• the CD4:CD8 T cell ratio in the periphery is over 2.5 at six months of age
• shift in ratio is evident at six weeks of age and lasts through 12 months of age
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• CD44hi CD62Llo memory T cells are increased about 3-fold at 6 months of age compared to controls
• differences are noticeable at 2 months of age with increases progressing with age
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• an increased percentage of B cells express the activation marker CD69 in vivo at 6 months of age
• a larger percentage of B cells express CD69 than controls in response to stimulation in vitro
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• follicular B cells are hyper-responsive to stimulation in vitro
• a similar phenotype is observed in mice homozygous for just the Ptprctm1Weis allele
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• the activation marker CD69 is upregulated on both CD4 and CD8 T cells in vivo
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• double-positive thymocytes are hyper-responsive to in vitro stimulation
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• lymphadenopathy is observed as early as 8 weeks of age
• is progressive with time and greatly exceeds the mild lymphoproliferation evident in each of the single mutants
• cell counts are variable with some counts being 10-fold higher than controls at six months of age
• lymphadenopathy is generally out of proportion to the degree of splenomegaly observed
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• auto-IgG antibodies are detected in some mice starting at 3 months of age
• by 9 months of age, auto-antibodies titers can reach levels observed in MRL/Lpr mice
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• perivascular infiltrates occur in the liver of mice over 12 months of age
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• kidneys of 12 month old mice have perivascular lymphocytic infiltrates, interstitial lymphocytic infiltrates, and hypercellular glomeruli with evidence of segmental sclerosis
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• perivascular infiltrates occur in the lung of mice over 12 months of age
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renal/urinary system
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• mice over 12 months of age have variable degrees of proteinuria
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• kidneys of 12 month old mice have perivascular lymphocytic infiltrates, interstitial lymphocytic infiltrates, and hypercellular glomeruli with evidence of segmental sclerosis
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• kidneys of 12 month old mice have hypercellular glomeruli with evidence of segmental sclerosis
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• kidneys from mice over 12 months of age are pale and nodular
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homeostasis/metabolism
liver/biliary system
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• perivascular infiltrates occur in the liver of mice over 12 months of age
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respiratory system
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• perivascular infiltrates occur in the lung of mice over 12 months of age
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hematopoietic system
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• double-positive thymocytes have CD5 and CD69 upregulated and are hyper-responsive to in vitro stimulation
|
|
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• T1 and T2 B cell numbers are increased in the spleen similar to mice homozygous for just the Ptprctm1Weis allele
|
|
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• follicular B cell numbers are reduced by about a third compared to controls
• a similar phenotype is observed in mice homozygous for just the Ptprctm1Weis allele
|
|
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• plasma cell numbers in the spleen is increased 4-fold at 3 months of age compared to controls
• a similar phenotype is observed in mice homozygous for just the Ptprctm1Weis allele
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|
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• the CD4:CD8 T cell ratio in the periphery is over 2.5 at six months of age
• shift in ratio is evident at six weeks of age and lasts through 12 months of age
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• CD44hi CD62Llo memory T cells are increased about 3-fold at 6 months of age compared to controls
• differences are noticeable at 2 months of age with increases progressing with age
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• an increased percentage of B cells express the activation marker CD69 in vivo at 6 months of age
• a larger percentage of B cells express CD69 than controls in response to stimulation in vitro
|
|
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• follicular B cells are hyper-responsive to stimulation in vitro
• a similar phenotype is observed in mice homozygous for just the Ptprctm1Weis allele
|
|
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• the activation marker CD69 is upregulated on both CD4 and CD8 T cells in vivo
|
|
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• double-positive thymocytes are hyper-responsive to in vitro stimulation
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endocrine/exocrine glands
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• double-positive thymocytes are hyper-responsive to in vitro stimulation
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Analysis Tools