Overview

Also Known As:E2F2 KO

These E2f2 knock-out mice exhibit a diffuse autoimmune disease that resembles systemic lupus erythematosus (SLE).

Donating Investigator

Ana Zubiaga, University of the Basque Country

Genetic overview

Genetic Background	Generation

E2f2^tm1Zubi

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	E2f2	E2F transcription factor 2

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Research Applications

Immunology, Inflammation and Autoimmunity Research
Cancer Research
Research Tools
Apoptosis Research
Developmental Biology Research
Internal/Organ Research
Hematological Research
Mouse/Human Gene Homologs

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice that are homozygous for the targeted mutation are viable and normal in size. No gene product, mRNA or protein, was detected. At age 15 months mutant mice have a 27% survival rate due to diffuse autoimmune disease that resembles systemic lupus erythematosus (SLE). The phenotype includes splenomegaly by 8-12 weeks of age, glomerulonephritis, accumulated inflammatory infiltrates in the lung, liver, and skin abnormalities such as hair loss, skin wounds, erythema. Anti-dsDNA antibodies are detected in the serum. There are an increased number of mature CD8+ thymocytes and an abnormal accumulation of CD8+ Cd44high Cd69- T effector/memory cells that are autoreactive in peripheral lymphoid organs. E2F2 deficient mice appear to have normal negative selection of thymocytes but demonstrate defects in peripheral tolerance of T lymphoctes (especially Cd8+ T cells) leading to progressive autoimmune disease. This mutant mouse strain may be useful in studies of autoimmunity and may serve as model of systemic lupus erythematosus.

Development

A targeting vector containing neomycin resistance and thymidine kinase genes was used to disrupt the second exon which encodes the DNA binding and dimerization domains of the protein. The construct was electroporated into 129S1/Sv-p+Tyr+Kitl+ derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to C57BL/6 mice.

Selected References

Murga M; Fernandez-Capetillo O; Field SJ; Moreno B; Borlado LR; Fujiwara Y; Balomenos D; Vicario A; Carrera AC; Orkin SH; Greenberg ME; Zubiaga AM. 2001. Mutation of E2F2 in mice causes enhanced T lymphocyte proliferation, leading to the development of autoimmunity. Immunity 15(6):959-70PubMed: 11754817 MGI: J:76318

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Genetics

E2f2^tm1Zubi

Allele Symbol: E2f2^tm1Zubi

Allele Name	targeted mutation 1, Ana Zubiaga
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	E2F2^-; E2f2^tm1Gle
Gene Symbol and Name	E2f2, E2F transcription factor 2
Gene Synonym(s)
Strain of Origin	129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Chromosome	4
Molecular Note	A PGK-neo cassette was inserted into exon 3. Southern and Northern analysis was utilized to confirm the targeting event and lack of transcript in homozygous mutant animals, respectively.
Mutations Made By	Ana Zubiaga, University of the Basque Country

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: E2f2^tm1Zubi related

Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
  - lupus erythematosus
- T Cell Receptor Signaling Defects
  - B and T cell deficiency
- Lymphoid Tissue Defects
  - hematopoietic development
  - B and T cell deficiency
  - myeloid hyperplasia
- Immunodeficiency
  - T cell deficiency
- Inflammation
Cancer Research
- Increased Tumor Incidence
  - Lymphomas
  - Lymphomas: thymic
  - Lymphomas: B cell lymphomas
- Genes Regulating Growth and Proliferation
Research Tools
- Genetics Research
  - Mutagenesis and Transgenesis
  - Mutagenesis and Transgenesis: transcriptional activation
  - Mutagenesis and Transgenesis: Production of Targeted Mutations (Knockouts)
- Immunology, Inflammation and Autoimmunity Research
  - T cell deficiency
  - B cell lymphomas
- Cancer Research
  - B and T cell deficiency, xenograft/transplant host
  - genes regulating lymphoma development
- Apoptosis Research
- Hematological Research
Apoptosis Research
- Endogenous Regulators
  - Autoimmune Lymphroliferatve syndrome
Developmental Biology Research
- Lymphoid Tissue Defects
  - hematopoietic defects
Internal/Organ Research
- Thymus Defects
  - B and T cell deficient
- Lymphoid Tissue Defects
  - T cell deficiency
- Spleen Defects
Hematological Research
- Immunological Defects
  - B and T cell deficiency
- Hematopoietic Defects
Mouse/Human Gene Homologs
- systemic lupus erythematosus
Cell Biology Research
- Cell Cycle Regulation
- Genes Regulating Growth and Proliferation
Dermatology Research
- Skin and Hair Texture Defects

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: E2f2^tm1Zubi/E2f2^tm1Zubi
involves: 129S1/Sv * C57BL/6

cellular phenotype

abnormal cell death
- cell death induced by Myc expression in primary fibroblast cells is somewhat less efficient than in wild-type primary fibroblast

abnormal cell physiology
- adenovirus-Myc fails to induce S phase as it does in wild-type mouse embryonic fibroblasts

increased T cell proliferation
- in response to IL-2 treatment, effector/memory cell (CD44^hiCD69-) T cell proliferation is increased relative to in wild-type mice by 2 times at weeks 8 to 12, and 13 times at 15 months
- T cell proliferation stimulated by CD3 antibody is increased compared to in stimulated wild-type mice and is more prominent at suboptimal CD3 antibody concentrations

immune system phenotype

abnormal immune system morphology

abnormal immune system physiology

abnormal spleen white pulp morphology
- at 15 months, mice display white pulp hyperplasia and increased sinusoidal cellularity

abnormal T cell differentiation
- the fraction of mature (CD4+ and, especially, CD8+) thymocytes in the thymus is increased with a decreased in immature double positive thymocytes

abnormal T cell subpopulation ratio
- Normal - however, the T to B cells ratio is normal
- there is an increase in the number of CD8+ T cells relative to CD4+ T cells (CD4+/CD8+ ratio: 0.79+/-0.1 compared to 1.43+/-0.3 in wild-type mice)

enlarged spleen
- at 15 months, mice exhibit splenomegaly with spleen size 2 to 5 times greater than that of wild-type mice

glomerulonephritis
- affected glomeruli are enlarged with a thickened basement membrane and contain perivascular aggregates of inflammatory infiltrate and immune complex deposition
- elderly mice exhibit membranoproliferative glomerulonephritis that is focal and of moderate intensity

increased anti-double stranded DNA antibody level
- the amount of double stranded DNA antibodies is increased relative to in wild-type mice and corresponds to the severity of organ damage

increased inflammatory response
- at 15 months, mice exhibit features of autoimmune disease
- in elderly mice, increased mononuclear infiltrate is observed in the lung, kidney and liver

increased memory T cell number
- at 3 to 4 weeks and at 15 months, the number of CD44^hiCD69- memory T cells is increased

increased spleen weight
- at week 8 to 12, spleen weight is increased 2-fold (1445+/-250 mg) relative to in wild-type mice (668+/-108 mg) and continues to increase at 15 months (3340+/-540 mg compared to 722+/-125 mg in wild-type mice)

increased susceptibility to autoimmune disorder
- at 15 months, mice exhibit features of autoimmune disease including inflammatory infiltrate, adnormal accumulation of effector/memory T cells, and double stranded DNA antibodies

increased T cell proliferation
- in response to IL-2 treatment, effector/memory cell (CD44^hiCD69-) T cell proliferation is increased relative to in wild-type mice by 2 times at weeks 8 to 12, and 13 times at 15 months
- T cell proliferation stimulated by CD3 antibody is increased compared to in stimulated wild-type mice and is more prominent at suboptimal CD3 antibody concentrations

liver inflammation
- in elderly mice, inflammatory infiltrate accumulates in the liver and perivascular infiltrates are observed

lung inflammation
- in elderly mice, inflammatory infiltrate accumulates in the lung

integument phenotype

abnormal skin morphology
- elderly mice exhibit skin wounds

progressive hair loss
- elderly mice exhibit considerable hair loss

reddish skin
- elderly mice exhibit erythema affecting the head and neck

liver/biliary system phenotype

liver inflammation
- in elderly mice, inflammatory infiltrate accumulates in the liver and perivascular infiltrates are observed

mortality/aging

premature death
- at 15 months, only 27% of mice are alive compared to 67% of wild-type mice

renal/urinary system phenotype

glomerulonephritis
- affected glomeruli are enlarged with a thickened basement membrane and contain perivascular aggregates of inflammatory infiltrate and immune complex deposition
- elderly mice exhibit membranoproliferative glomerulonephritis that is focal and of moderate intensity

increased renal glomerulus basement membrane thickness
- affected glomeruli display a thickened basement membrane

renal glomerular immunoglobulin deposits

renal glomerulus hypertrophy
- affected glomeruli are enlarged

respiratory system phenotype

lung inflammation
- in elderly mice, inflammatory infiltrate accumulates in the lung

growth/size/body region phenotype

enlarged spleen
- at 15 months, mice exhibit splenomegaly with spleen size 2 to 5 times greater than that of wild-type mice

increased spleen weight
- at week 8 to 12, spleen weight is increased 2-fold (1445+/-250 mg) relative to in wild-type mice (668+/-108 mg) and continues to increase at 15 months (3340+/-540 mg compared to 722+/-125 mg in wild-type mice)

hematopoietic system phenotype

abnormal spleen white pulp morphology
- at 15 months, mice display white pulp hyperplasia and increased sinusoidal cellularity

abnormal T cell differentiation
- the fraction of mature (CD4+ and, especially, CD8+) thymocytes in the thymus is increased with a decreased in immature double positive thymocytes

abnormal T cell subpopulation ratio
- Normal - however, the T to B cells ratio is normal
- there is an increase in the number of CD8+ T cells relative to CD4+ T cells (CD4+/CD8+ ratio: 0.79+/-0.1 compared to 1.43+/-0.3 in wild-type mice)

enlarged spleen
- at 15 months, mice exhibit splenomegaly with spleen size 2 to 5 times greater than that of wild-type mice

increased memory T cell number
- at 3 to 4 weeks and at 15 months, the number of CD44^hiCD69- memory T cells is increased

increased spleen weight
- at week 8 to 12, spleen weight is increased 2-fold (1445+/-250 mg) relative to in wild-type mice (668+/-108 mg) and continues to increase at 15 months (3340+/-540 mg compared to 722+/-125 mg in wild-type mice)

increased T cell proliferation
- in response to IL-2 treatment, effector/memory cell (CD44^hiCD69-) T cell proliferation is increased relative to in wild-type mice by 2 times at weeks 8 to 12, and 13 times at 15 months
- T cell proliferation stimulated by CD3 antibody is increased compared to in stimulated wild-type mice and is more prominent at suboptimal CD3 antibody concentrations

References

Murga M; Fernandez-Capetillo O; Field SJ; Moreno B; Borlado LR; Fujiwara Y; Balomenos D; Vicario A; Carrera AC; Orkin SH; Greenberg ME; Zubiaga AM. 2001. Mutation of E2F2 in mice causes enhanced T lymphocyte proliferation, leading to the development of autoimmunity. Immunity 15(6):959-70PubMed: 11754817 MGI: J:76318

Additional References

Wu L; Timmers C; Maiti B; Saavedra HI; Sang L; Chong GT; Nuckolls F; Giangrande P; Wright FA; Field SJ; Greenberg ME; Orkin S; Nevins JR; Robinson ML; Leone G. 2001. The E2F1-3 transcription factors are essential for cellular proliferation. Nature 414(6862):457-62PubMed: 11719808 MGI: J:73374
Zhu JW; Field SJ; Gore L; Thompson M; Yang H; Fujiwara Y; Cardiff RD; Greenberg M; Orkin SH; DeGregori J. 2001. E2F1 and E2F2 Determine Thresholds for Antigen-Induced T-Cell Proliferation and Suppress Tumorigenesis. Mol Cell Biol 21(24):8547-64PubMed: 11713289 MGI: J:72952

Additional - E2f2^tm1Zubi related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:E2f2
- Genotyping resources and troubleshooting
Breeding Considerations

This strain originated on a B6;129 background and is maintained on the same as a homozygote.
- Additional Breeding and Husbandry Support
Citation
When using the E2F2 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004338 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
	Homozygous for B6;129-E2f2<tm1Zubi>

Related Products and Services

Frozen Mouse Embryo	B6;129-E2f2<tm1Zubi>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6;129-E2f2<tm1Zubi>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6;129-E2f2<tm1Zubi>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6;129-E2f2<tm1Zubi>/J Frozen Embryos	$3373.50

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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:E2F2 KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Selected References

E2f2tm1Zubi

Allele Symbol: E2f2tm1Zubi

Disease Terms

Research Areas By Phenotype

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

Genotype: E2f2tm1Zubi related

Mammalian Phenotype Terms by Genotype

Genotype: E2f2tm1Zubi/E2f2tm1Zubiinvolves: 129S1/Sv * C57BL/6

cellular phenotype

immune system phenotype

integument phenotype

liver/biliary system phenotype

mortality/aging

renal/urinary system phenotype

respiratory system phenotype

growth/size/body region phenotype

hematopoietic system phenotype

References

Additional References

Additional - E2f2tm1Zubi 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

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

E2f2^tm1Zubi

Allele Symbol: E2f2^tm1Zubi

Genotype: E2f2^tm1Zubi related

Genotype: E2f2^tm1Zubi/E2f2^tm1Zubi
involves: 129S1/Sv * C57BL/6

Additional - E2f2^tm1Zubi related