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, Gladstone Institute of Neurological Disease
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.
Neuronal ApoE expression is widespread in the brain. Expression of ApoE3 protected against excitotoxin (kainic acid)-induced neuronal damage (loss of synaptophysin-positive presynaptic terminals and MAP2-positive neuronal dendrites in the neocortex and hippocampus, and a disruption of neurofilament-positive axons in the hippocampus).
Available though Robert Mahley.
- Buttini M, Orth M, Bellosta S, Akeefe H, Pitas RE, Wyss-Coray T, Mucke L, Mahley RW. 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.
- Harris FM, Brecht WJ, Xu Q, Mahley RW, Huang Y. 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.
- Brecht WJ, Harris FM, Chang S, Tesseur I, Yu GQ, Xu Q, Dee Fish J, Wyss-Coray T, Buttini M, Mucke L, Mahley RW, Huang Y. 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.
- Buttini M, Akeefe H, Lin C, Mahley RW, Pitas RE, Wyss-Coray T, Mucke L. Dominant negative effects of apolipoprotein E4 revealed in transgenic models of neurodegenerative disease. Neuroscience. 2000;97(2):207-10. PubMed.