B6;129-E2f2^tm1Zubi/J

Stock number: 004338
Product name: E2F2 KO
Research areas: Apoptosis Research, Cancer Research, Cell Biology Research, Dermatology Research, Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Mouse/Human Gene Homologs, Research Tools

Description

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

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.

Allele

Symbol: E2f2^tm1Zubi
Name: targeted mutation 1, Ana Zubiaga
MGI accession ID: MGI:2179111
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: E2f2
Marker name: E2F transcription factor 2
Chromosome: 4
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
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.