This Pon3 knock-out strain exhibits altered liver lipid levels and increased mortality on a cholate-cholesterol diet. These mice may be suitable for use in studies of atherosclerosis and obesity.
Aldons J. Lusis, University of California at Los Angeles
The targeted Pon3 gene encodes a glycoprotein enzyme that interacts with high density lipoprotein (HDL) and hydrolyzes lactones. These mice carry a knock-out allele of Pon3 in which exon 4 has been replaced by a NEO cassette. No gene product (mRNA or protein) is detected by qPCR or Western blot analysis of liver from homozygotes. No lovastatinase activity is detected in liver homogenates from homozygous mice. When fed a cholate-cholesterol diet (15.8% fat, 1.25% cholesterol, and 0.5% sodium cholate), female knock-out mice develop larger (60% increase) atherosclerotic lesion size; 65% survival; increased levels of plasma total cholesterol, cholesterol ester, unesterified cholesterol; and decreased liver triglyceride levels compared to wildtype controls.
Mice that are homozygous for the targeted mutation are viable and fertile.
During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.
A targeting vector containing a NEO cassette was used to disrupt exon 4. 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 crossed to C57BL/6J mice, and then backcrossed to C57BL/6J for 10 generations. Heterozygotes were intercrossed to generated homozygotes. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
|Allele Name||targeted mutation 1, Aldons J Lusis|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Pon3, paraoxonase 3|
|Strain of Origin||Not Specified|
|Molecular Note||No details provided. Western blot analysis confirmed the absence of protein expression in liver mitochondria.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Pon3KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #027311 in your Materials and Methods section.