Mice homozygous for the Apoetm1Unc mutation show a marked increase in total plasma cholesterol levels that are unaffected by age or gender. Fatty streaks in the proximal aorta are found at three 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.
Dr. Nobuyo Maeda, University of North Carolina at Chapel Hill
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Apoe | apolipoprotein E |
Mice homozygous for the Apoetm1Unc 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. Additional studies indicate that apoE-deficient mice have altered responses to stress, impaired spatial learning and memory, altered long term potentiation, and synaptic damage.
The Apoetm1Unc mutant strain was developed in the laboratory of Dr. Nobuyo Maeda at The University of North Carolina at Chapel Hill. The 129P2/OlaHsd-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. This C57BL/6J-congenic Apoetm1Unc strain was produced by backcrossing at least 10 generations to C57BL/6J inbred mice. These mice have black coat color.
Of note, previous to 1995, mice backcrossed 6 times (N6) to C57BL/6J mice were distributed solely. Mice from the N6 generation were homozygous for pink-eyed dilution p giving them pink eyes and a silver coat color. The E14Tg2a ES cell line carried this recessive mutation which remained linked to the targeted Apoe gene on Chromosome 7 at the N6 backcross generation. Mice from the N6 colony are no longer available for distribution [1995].
Allele Name | targeted mutation 1, University of North Carolina |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | AopE(-); apoE-; APOE KO; Apoetm1Un; apoE0; ApoE-KO; EKO; epsilon-; mE-; mEKO |
Gene Symbol and Name | Apoe, apolipoprotein E |
Gene Synonym(s) | |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 7 |
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. |
Mutations Made By | Dr. Nobuyo Maeda, University of North Carolina at Chapel Hill |
When using the ApoE KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #002052 in your Materials and Methods section.
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