Human apolipoprotein E allele-specific brain expressing transgenic mice

Transgenic mice were created using human apolipoprotein E2, E3, and E4 gene fragments driven by the human glial acidic fibrillary protein (GFAP) promo ter. Founders were obtained and progeny were assayed for transgene expressi on in the brain by RNase protection, immunohistochemistry, and Western blot ting, demonstrating robust apolipoprotein E (apoE) brain expression, with h uman apoE representing up to similar to 0.2% of total brain protein. Select ed lines were bred to apoE-deficient mice yielding mice which expressed the human transgenic apoE isoforms in the absence of endogenous apoE. Immunohi stochemistry revealed accumulation of the transgene encoded human apoE thro ughout the, brain. Double immunofluorescence showed co-expression of the ap oE transgene with endogenous glial acidic fibrillary protein. Primary astro cyte cultures from the transgenic mice secreted human apoE into the medium. Aged apoE4 transgenic mouse brain failed to demonstrate any evidence of se nile plaques. These mice may be useful for elucidation of the mechanism by which apoE4 is associated with Alzheimer's disease. (C) 1998 Elsevier Scien ce Inc.