These Pon1 knock-out mice exhibit a sensitivity to the toxic effects of the chlorpyrifos and its active form, chlorpyrifos oxon, a potent cholinesterase inhibitor.
Aldons J. Lusis, University of California at Los Angeles
Mice that are homozygous for this targeted allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No paraoxonase activity is detected in blood plasma. Homozygous animals are extremely sensitive to the toxic effects of the chlorpyrifos and its active form, chlorpyrifos oxon, a potent cholinesterase inhibitor. When fed a high-fat, high-cholesterol diet, homozygous mice are more susceptible to atherosclerosis when compared to wildtype littermates. In vitro studies indicate that high-density lipoproteins derived from homozygous animals are unable to prevent low-density lipoprotein oxidation. This mutant mouse strain represents a model that may be useful in studies related to toxicology (particularly insecticide poisoning) and factors regulating susceptibility to atherosclerosis.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 1. The construct was electroporated into 129X1/SvJ-derived RW-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were backcrossed to C57BL/6J mice. These mice have been backcrossed to C57BL/6J for at least seven generations (8/01).
|Allele Name||targeted mutation 1, Aldons J Lusis|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Pon1, paraoxonase 1|
|Strain of Origin||129X1/SvJ|
|Molecular Note||Exon 1 is disrupted with a neomycin resistance gene via homlogous recombination. Plasma from homozygous mutant animals did not demonstrate paraoxonase activity and did not contain protein product as assayed by Western blot.|
|Mutations Made By|| |
Aldons Lusis, University of California at Los Angeles
This strain originated on a B6;129X1 background and has been backcrossed to C57BL/6J for at least seven generations (8/01).
When using the PON1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004160 in your Materials and Methods section.