EXPRESSION IN MOUSE EMBRYOS AND IN ADULT-MOUSE BRAIN OF 3 MEMBERS OF THE AMYLOID PRECURSOR PROTEIN FAMILY, OF THE ALPHA-2-MACROGLOBULIN RECEPTOR LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN AND OF ITS LIGANDS APOLIPOPROTEIN-E, LIPOPROTEIN-LIPASE, ALPHA-2-MACROGLOBULIN AND THE 40,000-MOLECULAR-WEIGHT RECEPTOR-ASSOCIATED PROTEIN

We have analysed by northern blotting and by in situ hybridization the expression patterns of eight different genes during the second half o f mouse embryonic development and in adult mouse brain: we compared th e messenger RNA levels of amyloid precursor protein and of the two amy loid precursor protein-like proteins I and 2 and we have analysed expr ession of apolipoprotein E and of its main receptor in brain, the alph a-2-macroglobulin/low density lipoprotein receptor-related protein and three other ligands: the proteinase inhibitor alpha-2-macroglobulin, the modifying enzyme lipoprotein lipase and the 44,000 molecular weigh t heparin binding protein, a ligand of unknown function. During embryo genesis the temporal expression pattern differs considerably for the t hree members of the amyloid precursor proteins. Total embryo messenger RNA levels of amyloid precursor protein and amyloid precursor protein -like protein 2 increased progressively, while amyloid precursor prote in-like protein 1 messenger RNA showed a burst of synthesis between da ys 10 and 13 post-coitum. Significantly, expression of the alpha-2-mac roglobulin/low density lipoprotein receptor-related protein and of its associated protein, the 44,000 molecular weight heparin binding prote in, exhibited their most important increase very similar to that of am yloid precursor protein-like protein 1, between days 10 and 13 post-co itum. Apolipoprotein E, lipoprotein lipase and alpha-2-macroglobulin m essenger RNA levels in total embryos increased progressively, beginnin g most pronounced at days 13, 15 and 17, respectively. In mouse embryo s, in situ hybridization established amyloid precursor protein, amyloi d precursor protein-like protein 2 and alpha-2-macroglobulin/low densi ty lipoprotein receptor-related protein messenger RNA to be expressed in most organs, with the notable exception of the liver, while express ion of the other studied proteins was much more restricted. Among adul t mouse tissues, the genes investigated were expressed very prominentl y in brain, except for lipoprotein lipase and for the complete absence of alpha-2-macroglobulin messenger RNA. In adult mouse brain, the cor tex and hippocampus exhibited strong signals for most genes analysed. Exceptions are lipoprotein lipase and apolipoprotein E messenger RNAs, and the absent alpha-2-macroglobulin messenger RNA. Several interesti ng features, similarities as well as differences, between brain tissue sections hybridized with probes for amyloid precursor protein, amyloi d precursor protein-like proteins 1 and 2 and between alpha-2-macroglo bulin/low density lipoprotein receptor-related protein and heparin bin ding protein-44 were observed and are described. The results are furth er discussed in view of the known or anticipated physiological functio ns of the proteins examined and of their possible role in the etiology of Alzheimer's disease.