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Phenotypes Associated with This Genotype
Genotype
MGI:3842290
Allelic
Composition
Ptpn22tm2Achn/Ptpn22tm2Achn
Ptprctm1Weis/Ptprctm1Weis
Genetic
Background
B6.Cg-Ptprctm1Weis Ptpn22tm2Achn
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptpn22tm2Achn mutation (1 available); any Ptpn22 mutation (53 available)
Ptprctm1Weis mutation (3 available); any Ptprc mutation (189 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• 33% of mice die between 10 and 12 months of age
• likely cause of death is glomerulonephritis

growth/size/body
• 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
• double-positive thymocytes have CD5 and CD69 upregulated and are hyper-responsive to in vitro stimulation
• T1 and T2 B cell numbers are increased in the spleen similar to mice homozygous for just the Ptprctm1Weis allele
• 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
• 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
• 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
• 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
• 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
• follicular B cells are hyper-responsive to stimulation in vitro
• a similar phenotype is observed in mice homozygous for just the Ptprctm1Weis allele
• the activation marker CD69 is upregulated on both CD4 and CD8 T cells in vivo
• double-positive thymocytes are hyper-responsive to in vitro stimulation
• 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
• 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
• perivascular infiltrates occur in the liver of mice over 12 months of age
• kidneys of 12 month old mice have perivascular lymphocytic infiltrates, interstitial lymphocytic infiltrates, and hypercellular glomeruli with evidence of segmental sclerosis
• perivascular infiltrates occur in the lung of mice over 12 months of age

renal/urinary system
• mice over 12 months of age have variable degrees of proteinuria
• kidneys of 12 month old mice have perivascular lymphocytic infiltrates, interstitial lymphocytic infiltrates, and hypercellular glomeruli with evidence of segmental sclerosis
• kidneys of 12 month old mice have hypercellular glomeruli with evidence of segmental sclerosis
• kidneys from mice over 12 months of age are pale and nodular

homeostasis/metabolism
• mice over 12 months of age have variable degrees of proteinuria

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

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

hematopoietic system
• double-positive thymocytes have CD5 and CD69 upregulated and are hyper-responsive to in vitro stimulation
• T1 and T2 B cell numbers are increased in the spleen similar to mice homozygous for just the Ptprctm1Weis allele
• 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
• 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
• 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
• 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
• 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
• follicular B cells are hyper-responsive to stimulation in vitro
• a similar phenotype is observed in mice homozygous for just the Ptprctm1Weis allele
• the activation marker CD69 is upregulated on both CD4 and CD8 T cells in vivo
• double-positive thymocytes are hyper-responsive to in vitro stimulation

endocrine/exocrine glands
• double-positive thymocytes are hyper-responsive to in vitro stimulation


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
11/12/2024
MGI 6.24
The Jackson Laboratory