This Ctcf knockout strain is useful in studies of epigenetic regulation, tumorigenesis, and apoptosis in early embryogenesis.
Galina N. Filippova, Fred Hutchinson Cancer Research Center
The Ctcf gene encodes the 11-zinc finger protein, CCCTC-binding transcription factor which is involved in chromatin organization, gene insulation and transcriptional regulation, and is critical for early embryogenesis. These mice carry a knock out mutation of the Ctcf gene. Mice that are heterozygous for the targeted mutation on 129 background are viable and fertile, but are poor breeders. Homozygous null mice have an embryonic lethal phenotype, failing to develop past E4.5-5.5. No gene product (mRNA) is detected by RT-PCR analysis of homozygous E4.5 embryos. Heterozygotes on the C57BL/6 X 129S4/SvJaeSor F1 background exhibit DNA methylation changes genome wide and have a higher frequency of spontaneous and carcinogen-induced neoplasms in a broad range of tissues when compared to wildtype controls. By 100 weeks of age 80% of the heterozygous C57BL/6 X 129S4/SvJaeSor F1 mice spontaneously succumb to cancer compared to only 40% of wildtype controls. The Donating Investigator reports that the strain cannot be maintained on the C57BL/6 or BALB/c background, and that the strain is a poor breeder on the 129 background.
A targeting vector containing a floxed PGK-NEO cassette was used to disrupt exons 3 through 11, and part of exon 12. The construct was electroporated into 129S4/SvJaeSor derived AK7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were crossed to MORE (Mox2Cre) mice to excise the floxed NEO cassette. The mice were maintained on the 129S4/SvJaeSor genetic background. Upon arrival at The Jackson Laboratory, the mice were crossed to 129S1/SvImJ (Stock No. 002448) at least once to establish the colony.
|Allele Name||targeted mutation 1.1, Galina Filippova|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Ctcf, CCCTC-binding factor|
|Strain of Origin||129S4/SvJaeSor|
|Molecular Note||A floxed neomycin resistance cassette replaced exons 3 through 12. Cre-mediated recombination removed the selection cassette.|
When maintaining a live colony, heterozygous mice may be bred together, to wildtype siblings, or to 129S1/SvImJ (Stock No. 002448) inbred mice. Homozygotes are not viable. The Donating Investigator reports that the strain cannot be maintained on the C57BL/6 or BALB/c background, and that the strain is a poor breeder on the 129 background.
When using the Ctcf KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #022072 in your Materials and Methods section.