Research Models


Species: Mouse
Genes: APOE
Modification: APOE: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: Origin: C57BL/6J; backcrossed with murine APOE-null mice
Availability: Available through Robert Mahley

Modification Details

APOE3 minigene consisting of part of the untranslated exon 1, the first intron, and the first 6 bp of exon 2 from the human APOE gene, a fragment of human APOE cDNA contributing the entire APOE coding region, and a genomic segment representing exon 4 noncoding sequence and 112 bp of 3' untranslated region including the polyadenylation signal. There was a base change in exon 4 encoding cysteine (C) in APOE3 at amino acid position 112. The NSE-APOE transgene was injected into ICR one-cell embryos. The NSE-APOE3 line was crossed with APOE-/- mice (Taconic #APOE-M) to eliminate wild-type APOE alleles. After two generations the transgenic mice were crossed with APOE-/- mice (Jackson Labs: Stock# 2052) to generate NSE-APOE3 mice that were at least 75% C57BL/6J.


Human ApoE3 protected against the age-dependent neurodegeneration seen in APOE-/- mice.

Other Phenotypes

Neuronal ApoE expression is widespread in the brain. Expression of ApoE3 protected against kainic acid-induced neuronal damage, specifically loss of synaptophysin-positive presynaptic terminals and  MAP2-positive neuronal dendrites in the neocortex and hippocampus, and reduced disruption of neurofilament-positive axons in the hippocampus.


Available though Robert Mahley.


  1. Experiments involving Tg mice with human gene without the mouse gene will increasingly yeild more clear data like this paper.

    View all comments by Hiroshi Mori

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Other Citations

  1. Robert Mahley

External Citations

  1. Taconic #APOE-M
  2. Jackson Labs: Stock# 2052

Further Reading


  1. . Expression of human apolipoprotein E3 or E4 in the brains of Apoe-/- mice: isoform-specific effects on neurodegeneration. J Neurosci. 1999 Jun 15;19(12):4867-80. PubMed.
  2. . Increased tau phosphorylation in apolipoprotein E4 transgenic mice is associated with activation of extracellular signal-regulated kinase: modulation by zinc. J Biol Chem. 2004 Oct 22;279(43):44795-801. PubMed.
  3. . Neuron-specific apolipoprotein e4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice. J Neurosci. 2004 Mar 10;24(10):2527-34. PubMed.
  4. . Dominant negative effects of apolipoprotein E4 revealed in transgenic models of neurodegenerative disease. Neuroscience. 2000;97(2):207-10. PubMed.