HUMAN APOLIPOPROTEIN E2, E3, AND E4 ISOFORM-SPECIFIC TRANSGENIC MICE - HUMAN-LIKE PATTERN OF GLIAL AND NEURONAL IMMUNOREACTIVITY IN CENTRAL-NERVOUS-SYSTEM NOT OBSERVED IN WILD-TYPE MICE

Apolipoprotein E (apoE) and its three major alleles (APOE2, E3, and E4 ) have been implicated in Alzheimer's disease and other neurological d isorders. Little is known of the role apoE plays in normal brain funct ion and pathology. To create a model to study apoE in brain, we have g enerated APOE transgenic mice using microinjection of allele-specific human genomic fragments to establish founders which were then bred to APOE knockout mice lacking a functional mouse apoE protein, This allow s the study of apoE without interference from the endogenous mouse APO E gene. Results demonstrate that transgenic lines have been establishe d that transcribe and express apoE appropriately in brain, liver, and other tissues. High cholesterol levels found in APOE knockout mice are substantially corrected in the APOE transgenic lines, ApoE immunoreac tivity has been detected in glial cells and selected classes of neuron s in all three isoform-specific transgenics. This pattern of immunorea ctivity is similar to that observed in nonhuman primates and man, and contrasts with the strictly glial staining pattern of normal rodents. (C) 1996 Academic Press, Inc.