Characterization of transgenic mice expressing apolipoprotein E4(C112R) and apolipoprotein E4(L28P; C112R)

Apolipoprotein E (ApoE), which is genetically polymorphic, is a constituent of different lipoproteins. Two variants, ApoE4(C112R) and ApoE4(L28P; C112 R) have been linked to the risk of developing Alzheimer's disease. Transgen ic mice carrying ApoE4(C112R) (AD71) and ApoE4(L28P; C112R) (AD61) were gen erated and compared to wild-type mice. The use of glial fibrillary acidic p rotein as promoter led to transgene expression mainly in glial cells but al so in neurons. Transgene protein levels were approximately three-and-a-half -fold that of endogenous ApoE in the glial fibrillary acidic protein-ApoE4( C112R) (AD71) and nearly twofold in the glial fibrillary acidic protein-Apo E4(L28P; C112R) (AD61) mouse Lines. Neither transgenic mouse differed from wild-type in cognitive tests at the age of approximately one-and a-half yea rs. The locomotor activity of AD61 mice was similar to controls, whereas AD 71 mice exhibited a clearly reduced level of motor activity. Immunohistolog ical and biochemical brain protein analyses revealed no difference between strains. Thus, in the absence of morphological changes over-expression of ApoE4(C112 R) on a background of endogenous mouse ApoE, may result in behavioral defic its while for the ApoE4(L28P; C112R) transgene higher expression might be r equired or some compensatory mechanisms might protect these animals from th e behavioral abnormalities. (C) 2000 IBRO. Published by Elsevier Science Lt d. All rights reserved.