Posted 22 May 2005
Transgene: The apoE4 minigene consists of part of the untranslated exon 1 (from
the AvrII site), 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 aa 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 (TJL #2052) to generate
NSE-apoE4 mice that were at least 75% C57BL/6J.
Promoter: Rat neuron-specific enolase promoter
Mouse strain: Origin: C57BL/6J; Backcrossed with murine apoE-null mice, N>20
Neuronal apoE expression was widespread in the brains of these mice. Expression
of apoE4 did not protected against excitotoxin (Kainic acid)-induced neuronal damage.
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.
Licensing/academic distribution contact information:
Dr. Robert W. Mahley
Gladstone Institute of Neurological Disease
1650 Owens Street
San Francisco, CA 94158
Patents: Patent Number: 6,046,381; Title: Apolipoprotein E Transgenic Mice and Assay
Methods; Inventors: Mucke, L., Raber, J., Buttini, M., Mahley, R.W., Pitas, R.E.;
Filing Date: 4/30/1998; Issue Date: 4/4/2000
Raber J, Wong D, Buttini M, Orth M, Bellosta S, Pitas RE, Mahley RW, Mucke L. Isoform-specific
effects of human apolipoprotein E on brain function revealed in ApoE knockout mice:
increased susceptibility of females. Proc Natl Acad Sci U S A 95(18):10914-9, 1998.
Buttini, M., Orth, M., Bellosta, S., Akeefe, H., Pitas, R. E., Wyss-Coray, T., Mucke,
L. & Mahley, R. W. Expression of human apolipoprotein E3 or E4 in the brains of
Apoe-/- mice: isoform-specific effects on neurodegeneration. J. Neurosci. 19, 4867-4880,
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. 279(43):44795-801, 2004.
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.
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.