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; C112R) have been linked to the risk of developing Alzheimer's disease. Transgenic mice carrying ApoE4(C112R) (AD71) and ApoE4(L28P; C112R) (AD61) were generated and compared to wild-type mice. The use of glial fibrillary acidic protein as promoter led to transgene expression mainly in glial cells but also 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-ApoE4(L28P; C112R) (AD61) mouse lines. Neither transgenic mouse differed from wild-type in cognitive tests at the age of approximately one-and-a-half years. The locomotor activity of AD61 mice was similar to controls, whereas AD71 mice exhibited a clearly reduced level of motor activity. Immunohistological and biochemical brain protein analyses revealed no difference between strains.Thus, in the absence of morphological changes over-expression of ApoE4(C112R) on a background of endogenous mouse ApoE, may result in behavioral deficits while for the ApoE4(L28P; C112R) transgene higher expression might be required or some compensatory mechanisms might protect these animals from the behavioral abnormalities.
Huber
G
G
Pharma Division, Preclinical CNS Research, F. Hoffmann-La Roche Ltd, 4070 Basel, Switzerland. gerda.huber_trottman@roche.com
März
W
W
Martin
J R
JR
Malherbe
P
P
Richards
J G
JG
Sueoka
N
N
Ohm
T
T
Hoffmann
M M
MM
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics* / Q000378:metabolism; D009043:Motor Activity / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D019076:Transgenes / Q000235:genetics*
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms