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
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 transgenic line was crossed with APOE-/- mice (Taconic #APOE-M) to eliminate wild-type APOE alleles and then crossed with APOE-/- mice (The Jackson Lab: 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 seen primarily in females.
Neuronal ApoE expression was widespread in the brain. Expression of ApoE4 did not protect against kainic acid-induced neuronal damage.
Available though Robert Mahley.
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