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
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
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DOI：
10.1016/0306-4522(94)00555-j
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发表时间：
1995-04-01
期刊：
影响因子：
3.3
通讯作者：
VANDENBERGHE, H
中科院分区：
文献类型：
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作者：
LORENT, K;OVERBERGH, L;VANDENBERGHE, H
我们用Northern印迹和原位杂交分析了小鼠胚胎后半期和成年小鼠脑内八个不同基因的表达模式：比较了淀粉样前体蛋白和两种淀粉样蛋白样蛋白I和2的信使RNA水平，分析了载脂蛋白E及其主要受体、α-2-巨球蛋白/低密度脂蛋白受体相关蛋白和其他三种配体：蛋白酶抑制物α-2-巨球蛋白、修饰酶脂蛋白脂肪酶和44,000分子量肝素结合蛋白的表达。一种功能未知的配体。在胚胎发育过程中，淀粉样前体蛋白的三个成员的时间表达模式有很大的不同。胚胎中淀粉样前体蛋白和淀粉样蛋白样蛋白2的总信使RNA水平逐渐升高，而淀粉样前体蛋白1信使RNA的合成在胎盘后10天到13天出现暴发。值得注意的是，α-2-巨球蛋白/低密度脂蛋白受体相关蛋白及其相关蛋白44000分子量肝素结合蛋白的表达在出生后第10天至第13天表现出与淀粉样前体蛋白1非常相似的最重要的增长。小鼠胚胎中载脂蛋白E、脂蛋白脂肪酶和α-2-巨球蛋白信使RNA的表达水平逐渐升高，分别在第13、15和17天最明显。在小鼠胚胎中，原位杂交证实淀粉样前体蛋白、淀粉样前体蛋白2和α-2-巨球蛋白/低密度脂蛋白受体相关蛋白信使RNA在大多数器官中都有表达，除了肝脏外，其他蛋白的表达受到了更多的限制。在成年小鼠组织中，除了脂蛋白脂肪酶和完全缺乏α-2-巨球蛋白信使RNA外，其他基因在脑中的表达都非常显著。在成年小鼠的大脑中，大脑皮层和海马区对大多数被分析的基因都显示出强烈的信号。例外的是脂蛋白脂肪酶和载脂蛋白E信使RNA，以及缺失的α-2-巨球蛋白信使RNA。观察和描述了与淀粉样前体蛋白、淀粉样前体蛋白1和2的探针杂交的脑组织切片以及α-2巨球蛋白/低密度脂蛋白受体相关蛋白和肝素结合蛋白-44之间的一些有趣的特征、相似之处和不同之处。鉴于所研究的蛋白质的已知或预期的生理功能以及它们在阿尔茨海默病的病因中的可能作用，进一步讨论了结果。
We have analysed by northern blotting and by in situ hybridization the expression patterns of eight different genes during the second half of mouse embryonic development and in adult mouse brain: we compared the messenger RNA levels of amyloid precursor protein and of the two amyloid precursor protein-like proteins I and 2 and we have analysed expression of apolipoprotein E and of its main receptor in brain, the alpha-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 weight heparin binding protein, a ligand of unknown function.During embryogenesis the temporal expression pattern differs considerably for the three 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 protein-like protein 1 messenger RNA showed a burst of synthesis between days 10 and 13 post-coitum. Significantly, expression of the alpha-2-macroglobulin/low density lipoprotein receptor-related protein and of its associated protein, the 44,000 molecular weight heparin binding protein, exhibited their most important increase very similar to that of amyloid precursor protein-like protein 1, between days 10 and 13 post-coitum. Apolipoprotein E, lipoprotein lipase and alpha-2-macroglobulin messenger RNA levels in total embryos increased progressively, beginning most pronounced at days 13, 15 and 17, respectively.In mouse embryos, in situ hybridization established amyloid precursor protein, amyloid precursor protein-like protein 2 and alpha-2-macroglobulin/low density lipoprotein receptor-related protein messenger RNA to be expressed in most organs, with the notable exception of the liver, while expression of the other studied proteins was much more restricted.Among adult mouse tissues, the genes investigated were expressed very prominently in brain, except for lipoprotein lipase and for the complete absence of alpha-2-macroglobulin messenger RNA. In adult mouse brain, the cortex 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 interesting features, similarities as well as differences, between brain tissue sections hybridized with probes for amyloid precursor protein, amyloid precursor protein-like proteins 1 and 2 and between alpha-2-macroglobulin/low density lipoprotein receptor-related protein and heparin binding protein-44 were observed and are described.The results are further discussed in view of the known or anticipated physiological functions of the proteins examined and of their possible role in the etiology of Alzheimer's disease.