These E2f2 knock-out mice exhibit a diffuse autoimmune disease that resembles systemic lupus erythematosus (SLE).
Ana Zubiaga, University of the Basque Country
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | E2f2 | E2F transcription factor 2 |
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.
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.
Allele Name | targeted mutation 1, Ana Zubiaga |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | E2F2-; E2f2tm1Gle |
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 |
This strain originated on a B6;129 background and is maintained on the same as a homozygote.
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.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Homozygous for B6;129-E2f2<tm1Zubi> |
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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