These E2f1 (E2F transcription factor 1) knockout mice exhibit late onset testicular atrophy, degenerated seminiferous tubules, abnormal submaxillary and parotid salivary glands, abnormal cells in the pancreas, late-onset weight loss and spontaneous tumors in 19% to 34% of mice. This mutant mouse strain may be useful in studies of cancer and cell cycle research.
Dr. Lili Yamasaki, Columbia University
Homozygotes: Mice that are homozygous for the targeted mutation are viable and normal in size. Although testes appear normal at 2.5 months, by 9 months homozygous males exhibit testicular atrophy and empty, degenerated seminiferous tubules, although no decrease in Leydig cells is observed. Submaxillary and parotid salivary glands develop abnormally large and swollen cell nuclei and binucleate cells. Large nuclei and binucleate cells also are observed in the exocrine portion of the pancreas. Body weights are normal until 12 to 15 months of age when many mice develop dramatic weight loss. Spontaneous tumors develop in 19% to 34% of mice between 8 and 18 months of age suggesting a function for E2f1 in tumor suppression. Tumor types include, in order of frequency, reproductive tract sarcomas, lung tumors, lymphomas and other tumor types at lower frequencies.
This mutant mouse strain may be useful in studies of cancer and cell cycle research.
Heterozygote: Normal phenotype, although several heterozygotes develop rare reproductive tract sarcomas and lung adenocarcinomas.
A targeting vector containing neomycin resistance gene in the antisense direction was used to replace a portion of exon 2 (cyclin A binding) and all of exon 3 (DNA binding). The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6J and offspring were maintained by sibling mating. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Nicholas J Dyson|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||E2f1tm1Njd; targeted mutation 1, Nicholas J Dyson|
|Gene Symbol and Name||E2f1, E2F transcription factor 1|
|Gene Synonym(s)||RBAP1; RBP3; E2F-1; RBBP3|
|Strain of Origin||129S2/SvPas|
|Molecular Note||All of exon 2 and part of exon 3, encoding residues critical for cyclin and DNA binding, was replaced with a neomycin cassette in antisense orientation. Immunoprecipitation and Western blot analysis demonstrated that no protein was made in fibroblasts isolated from E12.5 homozygous embryos.|
|Mutations Made By|| |
Dr. Lili Yamasaki, Columbia University
While maintaining a live colony, these mice are bred as heterozygotes or homozygous female x heterozygous male. Homozygous males are infertile.
When using the B6;129S2-E2f1tm1Njd/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34309 in your Materials and Methods section.
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