STOCK Apoe^tm1Unc/J

Stock number: 007069
Research areas: Cardiovascular Research, Metabolism Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

Mice homozygous for this Apoe (apolipoprotein E) targeted mutation, Apoe^tm1Unc, may be useful for studying impaired immune response, lipid and leptin homeostasis, atherosclerosis, hematopoiesis, hearing loss, xanthoma, behavior and learning defects, neurodegeneration, Alzheimer's Disease and diet-induced obesity without diabetes.

Detailed description

Mice homozygous for the Apoe^tm1Unc mutation show a marked increase in total plasma cholesterol levels that are unaffected by age or sex. Fatty streaks in the proximal aorta are found at 3 months of age. The lesions increase with age and progress to lesions with less lipid but more elongated cells, typical of a more advanced stage of pre-atherosclerotic lesion. Moderately increased triglyceride levels have been reported in mice with this mutation on a mixed C57BL/6 x 129 genetic background. Aged APOE deficient mice (>17 months) have been shown to develop xanthomatous lesions in the brain consisting mostly of crystalline cholesterol clefts, lipid globules, and foam cells. Smaller xanthomas were seen in the choroid plexus and ventral fornix. Recent studies indicate that APOE deficient mice have altered responses to stress, impaired spatial learning and memory, altered long term potentiation, and synaptic damage.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing neomycin cassette was used to disrupt exon 3 of the targeted gene. The plasmid used is designated as pNMC109 and the founder line is T-89 in the primary reference. The construct was electroporated into 129P2/OlaHsd-derived E14Tg2a 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 12 generations. These B6.129P2-Apoe^tm1Unc/J (Stock No. 002052) mice were then backcrossed to AKR/J (Stock No. 000648) using a speed congenic protocol to produce this strain (see SNP note below).

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. 5 of the 27 markers throughout the genome were segregating between AKR/J and 129, suggesting an incomplete backcross.

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.