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
The ApoE4 minigene consists of part of the untranslated exon 1, the first intron, third 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 arginine (R) in ApoE4 at amino acid position 112. The NSE-ApoE4 transgene was injected into one-cell embryos (ICR strain). NSE-ApoE4 tg line was crossed with APOE -/- mice (Taconic #APOE-M) to eliminate wild-type APOE alleles. Then crossed with ApoE -/- mice (Jackson Labs: Stock# 2052) to generate NSE-ApoE4 mice that were at least 75 percent C57BL/6J.
NSE-ApoE4 mice showed impairments in learning a water maze task and in vertical exploratory behavior that increased with age and were seen primarily in females.
Neuronal ApoE expression was widespread in the brain. Expression of ApoE4 did not protect against excitotoxin (kainic acid)-induced neuronal damage.
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.