B6.129P2-Uts2^tm1Ags Apoe^tm1Unc/J

Stock number: 026016
Research areas: Cardiovascular Research, Metabolism Research, Mouse/Human Gene Homologs, Research Tools

Description

These Uts2 Apoe double knock-out mice exhibit less severe atherosclerosis and reduced serum cytokine/apdipokine levels when compared to Apoe knockout mice. They are suitable for use in applications related to the study of pathogenesis of and potential treatments for atherosclerosis.

Detailed description

The Uts2 gene encodes for a highly conserved vasoconstrictor (vasoactive) peptide. These mice carry a knock out mutation of the Uts2 gene in which half of exon 4 and all of exons 5 and 6 are replaced by lacZ and a Pgk-NEO cassette, as well as a knock out mutation for the Apoe gene. Mice that are homozygous for both targeted mutations are viable and fertile. Double knockout mice exhibit reduced serum cytokine and adipokine levels, less severe aortic atherosclerosis, reduced mean arterial blood pressure, and lower serum very-low-density lipoprotein–cholesterol when compared to the Apoe knock out mice.

Development

For the Uts2 mutant allele, a targeting vector containing IRES sequence, lacZ and a Pgk-NEO cassette was used to disrupt half of exon 4 and all of exons 5 and 6. The construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6J for 10 generations. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background. Heterozygotes were intercrossed to generate homozygotes. The Uts2r knock out mice were then crossed to Apoe knock out mice (see Stock No. 002052). The double mutant mice were intercrossed to produce mice homozygous for both targeted mutations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Uts2^tm1Ags
Name: targeted mutation 1, Adel Giaid Schwertani
MGI accession ID: MGI:5588699
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Uts2
Marker name: urotensin 2
Chromosome: 4
Strain of origin: 129P2/OlaHsd
Molecular note: A targeting vector containing an IRES sequence, lacZ and a Pgk-NEO cassette was used to disrupt half of exon 4 and all of exons 5 and 6.

Allele

Symbol: Apoe^tm1Unc
Name: targeted mutation 1, University of North Carolina
MGI accession ID: MGI:1857129
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Apoe
Marker name: apolipoprotein E
Chromosome: 7
Strain of origin: 129P2/OlaHsd
Molecular note: Insertion of a neomycin resistance cassette deleted part of exon 3 and part of intron 3 of the Apoe gene. Plasma from homozygous mutant mice gave no detectable immunoprecipitate by the Ouchterlony double immunodiffusion test using a rabbit antibody to rat APOE.