D2.129P2(B6)-Apoe^tm1Unc/J

Stock number: 007067
Research areas: Cardiovascular Research, Diabetes and Obesity Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

Mice homozygous for the Apoe^tm1Unc mutation on the DBA/2J background may be useful in studies of diet-induced obesity without diabetes, Alzheimer's Disease, neurodegeneration, atherosclerosis and hypercholesterolemia.

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

The Apoe^tm1Unc mutant strain was developed in the laboratory of Dr. Nobuyo Maeda at The University of North Carolina at Chapel Hill. The 129-derived E14Tg2a ES cell line was used. The plasmid used is designated as pNMC109 and the founder line is T-89 in the primary reference. The mice were backcrossed to C57BL/6J for 10 generation and then backcrossed to DBA/2J for 5 generations (using a speed congenic protocol) before being made homozygous.

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.