Overview

Also Known As:C45 E613R/129.F9, CD45 E613R

B, T, and myeloid cells in mice homozygous for this targeted point mutation are hyperresponsive to stimulation, and B cell development is skewed to the B1 cell lineage. A mild lymphoproliferative disorder is developed but mice develop low titer or no autoantibodies.

Donating Investigator

Dr. Arthur Weiss, University of California, San Francisco

Genetic overview

Genetic Background	Generation

Ptprc^tm1Weis

Allele Type	Gene Symbol	Gene Name
Targeted (Humanized sequence)	Ptprc	protein tyrosine phosphatase, receptor type, C

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Research Applications

Immunology, Inflammation and Autoimmunity Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for this targeted point mutation are viable and fertile. The phenotype of this mutation, which inactivates the inhibitory wedge of the protein, is dependent upon the genetic background. On the 129S6 background, B, T, and myeloid cells are hyperresponsive to stimulation at a biochemical and cellular level. B cell development is skewed to the B1 cell lineage. A mild lymphoproliferative disorder develops, but the autoantibodies associated with the mixed C57BL/6 and 129 background do not develop (or do so at low titer). Cell surface expression of the protein is indistinguishable from wildtype as determined by flow cytometry of hematpoietic lineages in bone marrow, lymph node, spleen, thymus, peritoneal lavage, and peripheral blood.

Development

A targeting vector carrying the glutamate 613 (E613R) mutation in exon 18 and a loxP-flanked neomycin resistance cassette in the downstream intron was transfected into 129X1/SvJ-derived JM-1 embryonic stem (ES) cells. Targeted clones were microinjected into C57BL/6 blastocysts and mice derived from the resultant lines were bred to a C57BL/6 background Actb-Cre transgenic mouse to eliminate the neomycin resistance cassette. This line was crossed to C57BL/6, and later backcrossed to 129S6/SvEvTac for nine generations by the donating laboratory.

Selected References

Majeti R; Xu Z; Parslow TG; Olson JL; Daikh DI; Killeen N; Weiss A. 2000. An inactivating point mutation in the inhibitory wedge of CD45 causes lymphoproliferation and autoimmunity. Cell 103(7):1059-70PubMed: 11163182 MGI: J:66501

View All References

Genetics

Ptprc^tm1Weis

Allele Symbol: Ptprc^tm1Weis

Allele Name	targeted mutation 1, Arthur Weiss
Allele Type	Targeted (Humanized sequence)
Allele Synonym(s)	CD45 E613R; Cd45^w; Wedge
Gene Symbol and Name	Ptprc, protein tyrosine phosphatase, receptor type, C
Gene Synonym(s)
Promoter	Ptprc, protein tyrosine phosphatase, receptor type, C, mouse, laboratory
Strain of Origin	129X1/SvJ
Chromosome	1
Molecular Note	To recapitulate a mutation in the orthologous human gene that disrupts the inhibitory wedge, a glutamate to arginine substitution at codon 613 (E613R) was engineered in exon 18 and incorporated at the endogenous locus via homolgous recombination. A single loxP site remained in intron 18 after the floxed neo cassette was excised.
Mutations Made By	Dr. Arthur Weiss, University of California, San Francisco

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

systemic lupus erythematosus

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
- Lymphoid Tissue Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Ptprc^tm1Weis/Ptprc⁺
involves: 129X1/SvJ * C57BL/6

hematopoietic system phenotype

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

homeostasis/metabolism phenotype

increased urine protein level
- 33% of mice exhibit abnormal proteinura by 26 weeks of age
- proteinura greater than 30 mg/dl is observed at 6 weeks of age

immune system phenotype

increased anti-double stranded DNA antibody level
- 25% of heterozygous mice express auto-antibodies as early as 18 weeks of age

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

increased susceptibility to autoimmune disorder
- autoimmune lupus nephritis with autoantibody production leading to renal failure

mortality/aging

premature death
- 25% of mutant mice have died by 50 weeks of age compared to none in the wild-type control group
- mice die prematurely from multiple pathologies starting as early as 15 weeks of age

renal/urinary system phenotype

increased urine protein level
- 33% of mice exhibit abnormal proteinura by 26 weeks of age
- proteinura greater than 30 mg/dl is observed at 6 weeks of age

Genotype: Ptprc^tm1Weis/Ptprc^tm1Weis
involves: 129X1/SvJ * C57BL/6

cellular phenotype

abnormal granulocyte differentiation
- granulopoiesis is increased in the bone marrow

homeostasis/metabolism phenotype

increased urine protein level
- by 22 weeks of age, 54% of mice exhibit abnormal proteinura
- proteinura greater than 30 mg/dl is observed at 6 weeks of age

digestive/alimentary phenotype

abnormal digestion
- some female mice with kidney problems have extended stomachs full of undigested food
- these mice appear extremely thin and lethargic

immune system phenotype

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

abnormal granulocyte differentiation
- granulopoiesis is increased in the bone marrow

abnormal immune system organ morphology

abnormal leukocyte cell number

abnormal T cell activation
- 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

enlarged lymph nodes
- 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

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

glomerulonephritis
- karyorrhexis was noted in a segmental pattern
- kidneys have interstitial nephritis characterized by the presence of numerous mononuclear cells, tubular epithelial cell injury, interstitial fibrosis, and edema
- numerous subendothelial and mesangial deposits of immunoglobulin proteins are visible, along with widespread epithelial cell foot process effacement
- the glomeruli exhibited increase cellularity, thickened capillary loops, and an increase in mesangial matrix

increased anti-double stranded DNA antibody level
- 63% of homozygous mice have anti-dsDNA antibodies
- auto-antibodies are detected as earlier as 9 weeks of age

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

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

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

increased plasmacytoid dendritic cell number
- increased plasmacytoid cells are found in the lymph nodes

increased spleen red pulp amount
- expansion of the red pulp is noted in mice over 15 weeks of age

increased spleen white pulp amount
- expansion of the white pulp is noted in mice over 15 weeks of age

increased susceptibility to autoimmune disorder
- autoimmune lupus nephritis with autoantibody production leading to renal failure

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

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

growth/size/body region phenotype

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

mortality/aging

premature death
- 43% of mutant mice have died by 50 weeks of age compared to none in the wild-type control group
- mice die prematurely from multiple pathologies starting as early as 15 weeks of age

renal/urinary system phenotype

glomerulonephritis
- karyorrhexis was noted in a segmental pattern
- kidneys have interstitial nephritis characterized by the presence of numerous mononuclear cells, tubular epithelial cell injury, interstitial fibrosis, and edema
- numerous subendothelial and mesangial deposits of immunoglobulin proteins are visible, along with widespread epithelial cell foot process effacement
- the glomeruli exhibited increase cellularity, thickened capillary loops, and an increase in mesangial matrix

increased urine protein level
- by 22 weeks of age, 54% of mice exhibit abnormal proteinura
- proteinura greater than 30 mg/dl is observed at 6 weeks of age

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

oliguria
- some mice suffer from oliguria shortly before dying

hematopoietic system phenotype

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

abnormal erythropoiesis
- erythropoiesis in the bone marrow is decreased

abnormal granulocyte differentiation
- granulopoiesis is increased in the bone marrow

abnormal leukocyte cell number

abnormal T cell activation
- 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

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

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

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

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

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

increased plasmacytoid dendritic cell number
- increased plasmacytoid cells are found in the lymph nodes

increased spleen red pulp amount
- expansion of the red pulp is noted in mice over 15 weeks of age

increased spleen white pulp amount
- expansion of the white pulp is noted in mice over 15 weeks of age

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

Genotype: Ptprc^tm1Weis/Ptprc^tm1Weis
B6.129X1-Ptprc

endocrine/exocrine gland phenotype

abnormal thymocyte activation
- double-positive thymocytes are more responsive to in vitro stimulation than controls

immune system phenotype

abnormal B cell activation
- a slightly increased percentage of B cells express the activation marker at 6 months of age

abnormal double-positive T cell morphology
- double-positive thymocytes have CD5 and CD69 slighlty upregulated and are more responsive to in vitro stimulation

abnormal follicular B cell physiology
- follicular B cells are hyper-responsive to stimulation in vitro

abnormal T cell activation
- na¿ve CD8 T cells are hyper-response to in vitro stimulation
- the activation marker CD69 is slightly upregulated on both CD4 and CD8 T cells in vivo

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

abnormal thymocyte activation
- double-positive thymocytes are more responsive to in vitro stimulation than controls

decreased follicular B cell number
- follicular B cells are hyper-responsive to stimulation in vitro

enlarged lymph nodes
- mild lymphadenopathy is observed in these mice

increased memory T cell number
- 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

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

increased transitional stage B cell number
- T1 and T2 B cell numbers are increased in the spleen

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

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

hematopoietic system phenotype

abnormal B cell activation
- a slightly increased percentage of B cells express the activation marker at 6 months of age

abnormal double-positive T cell morphology
- double-positive thymocytes have CD5 and CD69 slighlty upregulated and are more responsive to in vitro stimulation

abnormal follicular B cell physiology
- follicular B cells are hyper-responsive to stimulation in vitro

abnormal T cell activation
- na¿ve CD8 T cells are hyper-response to in vitro stimulation
- the activation marker CD69 is slightly upregulated on both CD4 and CD8 T cells in vivo

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

abnormal thymocyte activation
- double-positive thymocytes are more responsive to in vitro stimulation than controls

decreased follicular B cell number
- follicular B cells are hyper-responsive to stimulation in vitro

increased memory T cell number
- 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

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

increased transitional stage B cell number
- T1 and T2 B cell numbers are increased in the spleen

liver/biliary system phenotype

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

mammalian phenotype

immune system phenotype
- Normal - immunoreceptor tyrosine-based activation motif-mediated cytokine secretion in NK cells is normal

respiratory system phenotype

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

References

Majeti R; Xu Z; Parslow TG; Olson JL; Daikh DI; Killeen N; Weiss A. 2000. An inactivating point mutation in the inhibitory wedge of CD45 causes lymphoproliferation and autoimmunity. Cell 103(7):1059-70PubMed: 11163182 MGI: J:66501

Additional - Ptprc^tm1Weis related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Ptprc
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice are bred as heterozygotes or homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the CD45 E613R mouse strain in a publication, please cite the originating article(s) and include JAX stock #007172 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Ptprc<tm1Weis>

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Also Known As:C45 E613R/129.F9, CD45 E613R

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

Ptprctm1Weis

Allele Symbol: Ptprctm1Weis

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Ptprctm1Weis/Ptprc+involves: 129X1/SvJ * C57BL/6

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

mortality/aging

renal/urinary system phenotype

Genotype: Ptprctm1Weis/Ptprctm1Weisinvolves: 129X1/SvJ * C57BL/6

cellular phenotype

homeostasis/metabolism phenotype

digestive/alimentary phenotype

immune system phenotype

growth/size/body region phenotype

mortality/aging

renal/urinary system phenotype

hematopoietic system phenotype

Genotype: Ptprctm1Weis/Ptprctm1WeisB6.129X1-Ptprc

endocrine/exocrine gland phenotype

immune system phenotype

hematopoietic system phenotype

liver/biliary system phenotype

mammalian phenotype

respiratory system phenotype

References

Additional - Ptprctm1Weis related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Ptprc^tm1Weis

Allele Symbol: Ptprc^tm1Weis

Genotype: Ptprc^tm1Weis/Ptprc⁺
involves: 129X1/SvJ * C57BL/6

Genotype: Ptprc^tm1Weis/Ptprc^tm1Weis
involves: 129X1/SvJ * C57BL/6

Genotype: Ptprc^tm1Weis/Ptprc^tm1Weis
B6.129X1-Ptprc

Additional - Ptprc^tm1Weis related