MOLECULAR-CLONING AND CHARACTERIZATION OF A CDNA-ENCODING THE CEREBROVASCULAR AND THE NEURITIC PLAQUE AMYLOID PEPTIDES
MOLECULAR-CLONING AND CHARACTERIZATION OF A CDNA-ENCODING THE CEREBROVASCULAR AND THE NEURITIC PLAQUE AMYLOID PEPTIDES
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DOI：
10.1073/pnas.84.12.4190
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发表时间：
1987-06-01
影响因子：
11.1
通讯作者：
WISNIEWSKI, HM
中科院分区：
文献类型：
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作者：
ROBAKIS, NK;RAMAKRISHNA, N;WISNIEWSKI, HM
在阿尔茨海默病患者和唐氏综合症成人的血管壁和脑神经炎斑块中发现了大量淀粉样纤维沉积。我们使用淀粉样肽的氨基酸序列来合成针对编码该肽的基因的特异性寡核苷酸探针。当用该探针筛选人脑cDNA文库时，发现具有1.7-腺苷酸酶插入物的克隆，该插入物含有编码412个氨基酸残基的长开放阅读框，包括淀粉样肽的28个氨基酸。RNA凝胶印迹显示，阿尔茨海默病、唐氏综合征或没有明显神经系统疾病的个体的大脑中存在3.3-β-淀粉酶mRNA。Southern印迹显示，同源基因存在于人类、兔子、绵羊、仓鼠和小鼠的基因组DNA中，这表明该基因在哺乳动物进化过程中是保守的。人类21号染色体上相应基因组序列的定位表明阿尔茨海默病和唐氏综合征之间存在遗传关系，这可能解释了成年唐氏综合征患者早期出现大量神经炎斑块的原因。
Deposits of amyloid fibers are found in large numbers in the walls of blood vessels and in neuritic plaques in the brains of patients with Alzheimer disease and adults with Down syndrome. We used the amino acid sequence of the amyloid peptide to synthesize oligonucleotide probes specific for the gene encoding this peptide. When a human brain cDNA library was screened with this probe, a clone was found with a 1.7-kilobase insert that contains a long open reading frame coding for 412 amino acid residues including the 28 amino acids of the amyloid peptide. RNA gel blots revealed that a 3.3-kilobase mRNA species was present in the brains of individuals with Alzheimer disease, with Down syndrome, or with no apparent neurological disorders. Southern blots showed that homologous genes are present in the genomic DNA of humans, rabbits, sheep, hamsters, and mice, suggesting that this gene has been conserved through mammalian evolution. Localization of the corresponding genomic sequences on human chromosome 21 suggests a genetic relationship between Alzheimer disease and Down syndrome, and it may explain the early appearance of large numbers of neuritic plaques in adult Down syndrome patients.