Identification of upregulated genes in scrapie-infected brain tissue
Identification of upregulated genes in scrapie-infected brain tissue
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DOI：
10.1128/jvi.74.21.10245-10248.2000
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发表时间：
2000-11-01
影响因子：
5.4
通讯作者：
Baier, M
中科院分区：
文献类型：
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作者：
Riemer, C;Queck, I;Baier, M
羊瘙痒病和一般神经退行性疾病的发病机制仍然没有得到充分的理解，因此正在进行深入研究。有大量证据表明，神经胶质细胞的激活先于神经变性，因此可能在疾病的发展和进展中发挥重要作用。在患病的大脑中具有改变的表达模式的基因的鉴定可以在分子水平上提供对最终导致神经元损失的过程的洞察。通过抑制性消减杂交技术富集羊瘙痒病感染脑组织中的差异表达基因，进行分子克隆，并进一步表征。北方印迹和核苷酸测序证实了19个上调基因的身份，其中11个是未知的羊瘙痒病的影响。这19个基因中有相当数量的基因，即编码干扰素诱导蛋白10（IP-10）、2 '，5'-寡聚（A）合成酶、Mx蛋白、IIGP蛋白、主要组织相容性复合物I类和II类、补体和β（2）-微球蛋白的基因，可被干扰素（IFN）诱导，表明IFN应答是羊瘙痒症中基因激活的可能机制。在新发现的基因中，编码2 '，5'-oligo（A）合成酶的基因特别令人感兴趣，因为它可以通过RNase L激活导致神经元细胞的凋亡损失。此外，在疾病的相对早期阶段观察到趋化因子IP-10和B淋巴细胞趋化因子mRNA的上调，并在整个疾病发展过程中持续。
The pathogenesis of scrapie, and of neurodegenerative diseases in general, is still insufficiently understood and is therefore being intensely researched. There is abundant evidence that the activation of glial cells precedes neurodegeneration and may thus play an important role in disease development and progression. The identification of genes with altered expression patterns in the diseased brain may provide insight on the molecular level into the process which ultimately leads to neuronal loss. Differentially expressed genes in scrapie-infected brain tissue were enriched by the suppression subtractive hybridization technique, molecularly cloned, and further characterized. Northern blotting and nucleotide sequencing confirmed the identities of 19 upregulated genes, 11 of which were unknown to be affected by scrapie. A considerable number of these 19 genes, namely those encoding interferon-inducible protein 10 (IP-10), 2',5'-oligo(A) synthetase, Mx protein, IIGP protein, major histocompatibility complex classes I and II, complement, and beta(2)-microglobulin, were inducible by interferons (IFNs), suggesting that an IFN response is a possible mechanism of gene activation in scrapie. Among the newly found genes, that coding for 2',5'-oligo(A) synthetase is of special interest because it could contribute to the apoptotic loss of neuronal cells via RNase L activation. In addition, upregulation of the chemokine IP-10 and B-lymphocyte chemoattractant mRNAs was seen at relatively early stages of the disease and was sustained throughout disease development.