Phenotypes associated with this allele

• Allele Symbol: Ptpn22^tm2Achn
• Allele Name: targeted mutation 2, Andrew C Chan
• Allele ID: MGI:3043477
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ptpn22^tm2Achn/Ptpn22^tm2Achn	B6.Cg-Ptpn22^tm2Achn	MGI:3842292
hm2	Ptpn22^tm2Achn/Ptpn22^tm2Achn	involves: C57BL/6	MGI:3043479
cx3	Ptpn22^tm2Achn/Ptpn22^tm2Achn Ptprc^tm1Weis/Ptprc^tm1Weis	B6.Cg-Ptprc^tm1Weis Ptpn22^tm2Achn	MGI:3842290

Genotype
MGI:3842292

hm1

• Allelic Composition: Ptpn22^tm2Achn/Ptpn22^tm2Achn
• Genetic Background: B6.Cg-Ptpn22^tm2Achn

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

immune system

abnormal double-positive T cell morphology ( J:147129 )

• double-positive thymocytes have CD5 and CD69 slighlty upregulated and are more responsive to in vitro stimulation

abnormal T cell subpopulation ratio ( J:147129 )

• the CD4:CD8 T cell ratio in the periphery is over 1.5 at six months of age

increased memory T cell number ( J:147129 )

• CD44^hi CD62L^lo 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

abnormal T cell activation ( J:147129 )

• 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

abnormal thymocyte activation ( J:147129 )

• double-positive thymocytes are more responsive to in vitro stimulation than controls

enlarged lymph nodes ( J:147129 )

• mild lymphadenopathy is observed in these mice

hematopoietic system

abnormal double-positive T cell morphology ( J:147129 )

• double-positive thymocytes have CD5 and CD69 slighlty upregulated and are more responsive to in vitro stimulation

abnormal T cell subpopulation ratio ( J:147129 )

• the CD4:CD8 T cell ratio in the periphery is over 1.5 at six months of age

increased memory T cell number ( J:147129 )

• CD44^hi CD62L^lo 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

abnormal T cell activation ( J:147129 )

• 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

abnormal thymocyte activation ( J:147129 )

• double-positive thymocytes are more responsive to in vitro stimulation than controls

endocrine/exocrine glands

abnormal thymocyte activation ( J:147129 )

• double-positive thymocytes are more responsive to in vitro stimulation than controls

Genotype
MGI:3043479

hm2

• Allelic Composition: Ptpn22^tm2Achn/Ptpn22^tm2Achn
• Genetic Background: involves: C57BL/6

hematopoietic system

enlarged spleen ( J:90029 )

• homozygous mice older than 6 months develop enlarged spleens

increased B cell number ( J:90029 )

• associated with the increased germinal center formation is an increase in GL-7+ B cells and CD23+ follicular B cells

increased follicular B cell number ( J:90029 )

• an increase in CD23+ follicular B cells is seen

increased spleen germinal center number ( J:90029 )

• 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

increased IgE level ( J:90029 )

• serum levels of IgE are increased in homozygotes compared to wild-type mice

increased IgG1 level ( J:90029 )

• 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

increased IgG2a level ( J:90029 )

• serum levels of IgG2a are increased in homozygotes compared to wild-type mice

abnormal T cell physiology ( J:90029 )

• 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

immune system

enlarged spleen ( J:90029 )

• homozygous mice older than 6 months develop enlarged spleens

increased B cell number ( J:90029 )

• associated with the increased germinal center formation is an increase in GL-7+ B cells and CD23+ follicular B cells

increased follicular B cell number ( J:90029 )

• an increase in CD23+ follicular B cells is seen

increased spleen germinal center number ( J:90029 )

• 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

increased IgE level ( J:90029 )

• serum levels of IgE are increased in homozygotes compared to wild-type mice

increased IgG1 level ( J:90029 )

• 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

increased IgG2a level ( J:90029 )

• serum levels of IgG2a are increased in homozygotes compared to wild-type mice

abnormal T cell physiology ( J:90029 )

• 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

abnormal Peyer's patch germinal center morphology ( J:90029 )

• 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

enlarged lymph nodes ( J:90029 )

• homozygous mice older than 6 months develop enlarged lymph nodes

growth/size/body

enlarged spleen ( J:90029 )

• homozygous mice older than 6 months develop enlarged spleens

Genotype
MGI:3842290

cx3

• Allelic Composition: Ptpn22^tm2Achn/Ptpn22^tm2Achn; Ptprc^tm1Weis/Ptprc^tm1Weis
• Genetic Background: B6.Cg-Ptprc^tm1Weis Ptpn22^tm2Achn

mortality/aging

premature death ( J:147129 )

• 33% of mice die between 10 and 12 months of age

• likely cause of death is glomerulonephritis

growth/size/body

decreased body weight ( J:147129 )

• 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

immune system

abnormal double-positive T cell morphology ( J:147129 )

• double-positive thymocytes have CD5 and CD69 upregulated and are hyper-responsive to in vitro stimulation

abnormal lymphocyte cell number ( J:147129 )

increased transitional stage B cell number ( J:147129 )

• T1 and T2 B cell numbers are increased in the spleen similar to mice homozygous for just the Ptprc^tm1Weis allele

decreased follicular B cell number ( J:147129 )

• follicular B cell numbers are reduced by about a third compared to controls

• a similar phenotype is observed in mice homozygous for just the Ptprc^tm1Weis allele

increased plasma cell number ( J:147129 )

• 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 Ptprc^tm1Weis allele

abnormal T cell subpopulation ratio ( J:147129 )

• 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

increased memory T cell number ( J:147129 )

• CD44^hi CD62L^lo 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

abnormal B cell activation ( J:147129 )

• 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

abnormal follicular B cell physiology ( J:147129 )

• follicular B cells are hyper-responsive to stimulation in vitro

• a similar phenotype is observed in mice homozygous for just the Ptprc^tm1Weis allele

abnormal T cell activation ( J:147129 )

• the activation marker CD69 is upregulated on both CD4 and CD8 T cells in vivo

abnormal thymocyte activation ( J:147129 )

• double-positive thymocytes are hyper-responsive to in vitro stimulation

enlarged lymph nodes ( J:147129 )

• 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

increased autoantibody level ( J:147129 )

• 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

liver inflammation ( J:147129 )

• perivascular infiltrates occur in the liver of mice over 12 months of age

glomerulonephritis ( J:147129 )

• kidneys of 12 month old mice have perivascular lymphocytic infiltrates, interstitial lymphocytic infiltrates, and hypercellular glomeruli with evidence of segmental sclerosis

lung inflammation ( J:147129 )

• perivascular infiltrates occur in the lung of mice over 12 months of age

renal/urinary system

increased urine protein level ( J:147129 )

• mice over 12 months of age have variable degrees of proteinuria

glomerulonephritis ( J:147129 )

• kidneys of 12 month old mice have perivascular lymphocytic infiltrates, interstitial lymphocytic infiltrates, and hypercellular glomeruli with evidence of segmental sclerosis

glomerulosclerosis ( J:147129 )

• kidneys of 12 month old mice have hypercellular glomeruli with evidence of segmental sclerosis

pale kidney ( J:147129 )

• kidneys from mice over 12 months of age are pale and nodular

homeostasis/metabolism

increased urine protein level ( J:147129 )

• mice over 12 months of age have variable degrees of proteinuria

liver/biliary system

liver inflammation ( J:147129 )

• perivascular infiltrates occur in the liver of mice over 12 months of age

respiratory system

lung inflammation ( J:147129 )

• perivascular infiltrates occur in the lung of mice over 12 months of age

hematopoietic system

abnormal double-positive T cell morphology ( J:147129 )

• double-positive thymocytes have CD5 and CD69 upregulated and are hyper-responsive to in vitro stimulation

abnormal lymphocyte cell number ( J:147129 )

increased transitional stage B cell number ( J:147129 )

• T1 and T2 B cell numbers are increased in the spleen similar to mice homozygous for just the Ptprc^tm1Weis allele

decreased follicular B cell number ( J:147129 )

• follicular B cell numbers are reduced by about a third compared to controls

• a similar phenotype is observed in mice homozygous for just the Ptprc^tm1Weis allele

increased plasma cell number ( J:147129 )

• 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 Ptprc^tm1Weis allele

abnormal T cell subpopulation ratio ( J:147129 )

• 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

increased memory T cell number ( J:147129 )

• CD44^hi CD62L^lo 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

abnormal B cell activation ( J:147129 )

• 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

abnormal follicular B cell physiology ( J:147129 )

• follicular B cells are hyper-responsive to stimulation in vitro

• a similar phenotype is observed in mice homozygous for just the Ptprc^tm1Weis allele

abnormal T cell activation ( J:147129 )

• the activation marker CD69 is upregulated on both CD4 and CD8 T cells in vivo

abnormal thymocyte activation ( J:147129 )

• double-positive thymocytes are hyper-responsive to in vitro stimulation

endocrine/exocrine glands

abnormal thymocyte activation ( J:147129 )

• double-positive thymocytes are hyper-responsive to in vitro stimulation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic lupus erythematosus		DOID:9074	OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420	J:147129