These Ephx1 knock-out mice exhibit resistance to 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer.
Frank J Gonzalez, National Institutes of Health (NIH/NCI)
Mice that are homozygous null for the Ephx1 gene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No Ephx1 protein product is detected, although an aberrant transcript may be produced. Embryo-derived fibroblasts from homozygous mice are shown to be incapable of metabolizing the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Cells in culture display a resistance to the toxic effects of DMBA. Whole animals are completely resistant to DMBA-induced skin cancer. This mutant mouse strain represents a model that may be useful in studies related to metabolism of carcinogens.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt Ephx1 exon 2. The construct was electroporated into 129X1/SvJ derived embryonic stem (ES) cells from Genome Systems Inc. (St. Louis, MO). Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were crossed to female C57BL/6N mice.
|Allele Name||targeted mutation 1, Frank J Gonzalez|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Ephx1, epoxide hydrolase 1, microsomal|
|Strain of Origin||129X1/SvJ|
|General Note||The ES cell line, purchased from Genome Systems (St. Louis), was derived from 129X1/Sv. The name of the line was not specified.|
|Molecular Note||A neomycin resistance cassette replaced 0.7 kb of sequence containing part of exon 2. Northern blot analysis detected a shorter mRNA transcript produced by this allele. However, western blot analysis of extracts of liver microsomes derived from homozygous mice did not detect any encoded protein.|
|Mutations Made By|| |
Frank Gonzalez, National Institutes of Health (NIH/NCI)
This strain originated on a B6;129X1 background and has been backcrossed to C57BL/6N for four generations before being made homozygous.
When using the mEH KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004143 in your Materials and Methods section.