B6.129S6-Apoe^tm1.1Mae/MazzJ

Stock number: 028530
Product name: ApoE-Flox
Research areas: Cardiovascular Research, Metabolism Research, Neurobiology Research, Research Tools

Description

These floxed mutant mice possess loxP sites flanking exon 3 of the Apoe gene. This strain may be useful for generating conditional mutations in applications related to the regulation of lipoprotein and cholesterol metabolism, neurovascular function, inflammation and in the pathophysiology of neurodegenerative cardiovascular diseases.

Detailed description

A major function of apolipoprotein E (APOE) is mediation of lipid transport throughout various tissues and cells. Circulating APOE is associated with chylomicron and Intermediate-density lipoprotein (IDLs) and is mostly produced by the liver, although other tissues and cells, including adrenal gland, macrophages, vascular smooth muscle cells, and adipocytes, are also known to synthesize and secrete APOE. In the central nervous system, APOE is produced by glial cells, and by injured neurons and cells in the choroid plexus at a lower levels than observed in astrocytes. APOE is important in lipoprotein and cholesterol metabolism, neurovascular function, regulation of the immune system and in the pathophysiology of neurodegenerative diseases such as Alzheimer’s disease and cardiovascular diseases such as atherosclerosis. These mice possess loxP sites on either side of exon 3 of the targeted gene. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 3 deleted in the cre-expressing tissues. Removal of the floxed sequence creates a null allele.

When bred to a strain with Cre recombinase expression in adipose tissue (see Stock No. 005069 for example) to generate SEKO (selective apoE knockout- adipose tissue) mice, this mutant mouse strain may be useful in studies of lipid metabolism and adipose tissue inflammation.

Development

A targeting vector designed by Drs. Theodore Mazzone (University of Chicago) and Nobuyo Maeda (University of North Carolina, Chapel Hill) containing a FRT site flanked NEO cassette was utilized in the construction of this mutant. This selection cassette and a loxP site was inserted downstream of exon 3 of the targeted gene, and another loxP site was inserted upstream of exon 3. This construct was electroporated into 129S6/SvEvTac derived TC-1 embryonic stem (ES) cells which were transiently transfected with a FLP recombinase vector to remove the selection cassette. ES cells that had successfully undergone FLP recombination and no longer retained the selection cassette but did retain the loxP-flanked exon 3 were injected in blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were then backcrossed to C57BL/6J for 10 generations. 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

Symbol: Apoe^tm1.1Mae
Name: targeted mutation 1.1, Nobuyo Maeda
MGI accession ID: MGI:5703874
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Apoe
Marker name: apolipoprotein E
Chromosome: 7
Strain of origin: 129S6/SvEvTac
Molecular note: The targeting vector contains a loxP site and an FRT-flanked neo cassette inserted downstream of exon 3 of the targeted gene, and another loxP site inserted upstream of exon 3. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exon 3 floxed.