Phenotypes associated with this allele

• Allele Symbol: Ptprc^tm1Weis
• Allele Name: targeted mutation 1, Arthur Weiss
• Allele ID: MGI:3027340
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ptprc^tm1Weis/Ptprc^tm1Weis	B6.129X1-Ptprc^tm1Weis	MGI:3842291
hm2	Ptprc^tm1Weis/Ptprc^tm1Weis	involves: 129X1/SvJ * C57BL/6	MGI:3841485
ht3	Ptprc^tm1Weis/Ptprc^+	involves: 129X1/SvJ * C57BL/6	MGI:3841484
cx4	Ptpn22^tm2Achn/Ptpn22^tm2Achn Ptprc^tm1Weis/Ptprc^tm1Weis	B6.Cg-Ptprc^tm1Weis Ptpn22^tm2Achn	MGI:3842290

Genotype
MGI:3842291

hm1

• Allelic Composition: Ptprc^tm1Weis/Ptprc^tm1Weis
• Genetic Background: B6.129X1-Ptprc^tm1Weis

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

immune system

immune system phenotype ( J:109462 )

N • immunoreceptor tyrosine-based activation motif-mediated cytokine secretion in NK cells is normal

increased transitional stage B cell number ( J:147129 )

• T1 and T2 B cell numbers are increased in the spleen

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

decreased follicular B cell number ( J:147129 )

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

increased plasma cell number ( J:147129 )

• plasma cell numbers in the spleen is increased 4-fold at 3 months of age compared to controls

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 B cell activation ( J:147129 )

• a slightly increased percentage of B cells express the activation marker at 6 months of age

abnormal follicular B cell physiology ( J:147129 )

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

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

liver inflammation ( J:147129 )

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

lung inflammation ( J:147129 )

• perivascular infiltrates occur in the lung 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

liver/biliary system

liver inflammation ( J:147129 )

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

hematopoietic system

increased transitional stage B cell number ( J:147129 )

• T1 and T2 B cell numbers are increased in the spleen

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

decreased follicular B cell number ( J:147129 )

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

increased plasma cell number ( J:147129 )

• plasma cell numbers in the spleen is increased 4-fold at 3 months of age compared to controls

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 B cell activation ( J:147129 )

• a slightly increased percentage of B cells express the activation marker at 6 months of age

abnormal follicular B cell physiology ( J:147129 )

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

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:3841485

hm2

• Allelic Composition: Ptprc^tm1Weis/Ptprc^tm1Weis
• Genetic Background: involves: 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:66501 )

• mice die prematurely from multiple pathologies starting as early as 15 weeks of age

• 43% of mutant mice have died by 50 weeks of age compared to none in the wild-type control group

immune system

abnormal granulocyte differentiation ( J:66501 )

• granulopoiesis is increased in the bone marrow

abnormal leukocyte cell number ( J:66501 )

increased plasmacytoid dendritic cell number ( J:66501 )

• increased plasmacytoid cells are found in the lymph nodes

increased B cell number ( J:66501 )

• B cell numbers are increased in older mice 2- to 8- fold

increased T cell number ( J:66501 )

• T cell numbers are increased in older mice 2- to 8- fold

abnormal B cell activation ( J:66501 )

• B cells expressing activation markers are increased 26% in wild-type to 62% and 70%, in mild and severe lymphadenopathy, respectively

increased IgA level ( J:66501 )

• mean IgA levels are 35-fold higher than controls by 14 weeks of age

increased IgG2a level ( J:66501 )

• there is a 12-fold increase in IgG2a levels over controls in 14 week old mice

abnormal T cell activation ( J:66501 )

• T cells expressing activation markers are increased from 21% in wild-type to 34% in mice with mild lymphadenopathy, and 57% in mice with severe lymphadenopathy

abnormal immune system organ morphology ( J:66501 )

enlarged spleen ( J:66501 )

• spleens of mice over 15 weeks of age weigh 3-10 times as much as controls

increased spleen red pulp amount ( J:66501 )

• expansion of the red pulp is noted in mice over 15 weeks of age

increased spleen white pulp amount ( J:66501 )

• expansion of the white pulp is noted in mice over 15 weeks of age

enlarged lymph nodes ( J:66501 )

• 70% of mice over 15 weeks of age develop lymphadenopathy with about half the cases being severe

• generalized lymphadenopathy is observed in severe cases while lymphadenopathy is often confined to the cervical and submandibular lymph nodes in mild cases

lymph node hyperplasia ( J:66501 )

• lymph node cell numbers are 2- to 8- fold greater than controls in older mice with swollen lymph nodes

increased susceptibility to autoimmune disorder ( J:66501 )

• autoimmune lupus nephritis with autoantibody production leading to renal failure

increased anti-double stranded DNA antibody level ( J:66501 )

• 63% of homozygous mice have anti-dsDNA antibodies

• auto-antibodies are detected as earlier as 9 weeks of age

glomerulonephritis ( J:66501 )

• kidneys have interstitial nephritis characterized by the presence of numerous mononuclear cells, tubular epithelial cell injury, interstitial fibrosis, and edema

• the glomeruli exhibited increase cellularity, thickened capillary loops, and an increase in mesangial matrix

• karyorrhexis was noted in a segmental pattern

• numerous subendothelial and mesangial deposits of immunoglobulin proteins are visible, along with widespread epithelial cell foot process effacement

renal/urinary system

increased urine protein level ( J:66501 )

• proteinura greater than 30 mg/dl is observed at 6 weeks of age

• by 22 weeks of age, 54% of mice exhibit abnormal proteinura

glomerulonephritis ( J:66501 )

• kidneys have interstitial nephritis characterized by the presence of numerous mononuclear cells, tubular epithelial cell injury, interstitial fibrosis, and edema

• the glomeruli exhibited increase cellularity, thickened capillary loops, and an increase in mesangial matrix

• karyorrhexis was noted in a segmental pattern

• numerous subendothelial and mesangial deposits of immunoglobulin proteins are visible, along with widespread epithelial cell foot process effacement

kidney failure ( J:66501 )

• some mice suffer from oliguria shortly before dying suggesting kidney failure

oliguria ( J:66501 )

• some mice suffer from oliguria shortly before dying

digestive/alimentary system

abnormal digestion ( J:66501 )

• some female mice with kidney problems have extended stomachs full of undigested food

• these mice appear extremely thin and lethargic

hematopoietic system

abnormal granulocyte differentiation ( J:66501 )

• granulopoiesis is increased in the bone marrow

enlarged spleen ( J:66501 )

• spleens of mice over 15 weeks of age weigh 3-10 times as much as controls

abnormal erythropoiesis ( J:66501 )

• erythropoiesis in the bone marrow is decreased

extramedullary hematopoiesis ( J:66501 )

• along with numerous megakaryocytes, islands of erythropoiesis and granulopoiesis are observed throughout the enlarged spleens

abnormal leukocyte cell number ( J:66501 )

increased plasmacytoid dendritic cell number ( J:66501 )

• increased plasmacytoid cells are found in the lymph nodes

increased B cell number ( J:66501 )

• B cell numbers are increased in older mice 2- to 8- fold

increased T cell number ( J:66501 )

• T cell numbers are increased in older mice 2- to 8- fold

increased spleen red pulp amount ( J:66501 )

• expansion of the red pulp is noted in mice over 15 weeks of age

increased spleen white pulp amount ( J:66501 )

• expansion of the white pulp is noted in mice over 15 weeks of age

abnormal B cell activation ( J:66501 )

• B cells expressing activation markers are increased 26% in wild-type to 62% and 70%, in mild and severe lymphadenopathy, respectively

increased IgA level ( J:66501 )

• mean IgA levels are 35-fold higher than controls by 14 weeks of age

increased IgG2a level ( J:66501 )

• there is a 12-fold increase in IgG2a levels over controls in 14 week old mice

abnormal T cell activation ( J:66501 )

• T cells expressing activation markers are increased from 21% in wild-type to 34% in mice with mild lymphadenopathy, and 57% in mice with severe lymphadenopathy

homeostasis/metabolism

increased urine protein level ( J:66501 )

• proteinura greater than 30 mg/dl is observed at 6 weeks of age

• by 22 weeks of age, 54% of mice exhibit abnormal proteinura

cellular

abnormal granulocyte differentiation ( J:66501 )

• granulopoiesis is increased in the bone marrow

growth/size/body

enlarged spleen ( J:66501 )

• spleens of mice over 15 weeks of age weigh 3-10 times as much as controls

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:66501

Genotype
MGI:3841484

ht3

• Allelic Composition: Ptprc^tm1Weis/Ptprc⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:66501 )

• mice die prematurely from multiple pathologies starting as early as 15 weeks of age

• 25% of mutant mice have died by 50 weeks of age compared to none in the wild-type control group

immune system

increased IgG2a level ( J:66501 )

• there is a 12-fold increase in IgG2a levels over controls in 16 week old mice

increased susceptibility to autoimmune disorder ( J:66501 )

• autoimmune lupus nephritis with autoantibody production leading to renal failure

increased anti-double stranded DNA antibody level ( J:66501 )

• 25% of heterozygous mice express auto-antibodies as early as 18 weeks of age

renal/urinary system

increased urine protein level ( J:66501 )

• proteinura greater than 30 mg/dl is observed at 6 weeks of age

• 33% of mice exhibit abnormal proteinura by 26 weeks of age

homeostasis/metabolism

increased urine protein level ( J:66501 )

• proteinura greater than 30 mg/dl is observed at 6 weeks of age

• 33% of mice exhibit abnormal proteinura by 26 weeks of age

hematopoietic system

increased IgG2a level ( J:66501 )

• there is a 12-fold increase in IgG2a levels over controls in 16 week old mice

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:66501

Genotype
MGI:3842290

cx4

• 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