Microarray analysis of nonhuman primates:: validation of experimental models in neurological disorders

Microarray analysis of nonhuman primates:: validation of experimental models in neurological disorders
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DOI:
10.1096/fj.02-0681fje
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发表时间:
2003-03-01
期刊:
影响因子:
4.8
通讯作者:
Wong, G
Wong, G
中科院分区:
生物学2区
文献类型:
--
作者:
Marvanová, M;Ménager, J;Wong, G

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非人类灵长类动物(NHP)由于其相似的生理学特性,为许多人类相关疾病提供了强大的实验动物模型。尽管如此,艾滋病和阿尔茨海默氏症等重要疾病的获得、进展和结果仍然存在巨大差异,其根本原因仍不清楚。我们探索了人类高密度寡核苷酸阵列在调查 NHP 基因组转录谱中的效用。来自人类 (Homo sapiens)、普通黑猩猩 (Pan troglodytes)、食蟹猴 (Macaca fascicularis) 和普通狨猴 (Callithrix jacchus) 前额皮质的总 RNA 被标记并与 Affymetrix U95A GeneChip 探针阵列杂交。添加了之前从普通黑猩猩和猩猩(Pongo pygmaeus)获得的相应数据进行比较。定性(存在或未检测到)和定量(表达水平)分析表明,许多已知与人类神经系统疾病有关的基因在 NHP 中存在并受到调节。猕猴和狨猴中不存在参与多巴胺代谢的基因(儿茶酚-O-甲基转移酶)。与人类相比,NHP 中谷氨酸受体 2 上调,转录相关基因下调。我们证明 NHP 的转录谱分析可以提供比较基因组数据,以验证和更好地关注人类神经系统疾病的实验动物模型。
Nonhuman primates (NHPs) have provided robust experimental animal models for many human-related diseases due to their similar physiologies. Nonetheless, profound differences remain in the acquisition, progression, and outcome of important diseases such as AIDS and Alzheimer's, for which the underlying basis remains obscure. We explored the utility of human high-density oligonucleotide arrays to survey the transcription profile of NHP genomes. Total RNA from prefrontal cortices of human (Homo sapiens), common chimpanzee (Pan troglodytes), cynomolgous macaque (Macaca fascicularis), and common marmoset (Callithrix jacchus) was labeled and hybridized to Affymetrix U95A GeneChip probe arrays. Corresponding data obtained previously from common chimpanzee and orangutan (Pongo pygmaeus) were added for comparison. Qualitative (present or not detected) and quantitative (expression level) analysis indicated that many genes known to be involved in human neurological disorders were present and regulated in NHPs. A gene involved in dopamine metabolism (catechol-O-methyltransferase) was absent in macaque and marmoset. Glutamate receptor 2 was upregulated, and transcription-associated genes were down-regulated in NHPs compared with humans. We demonstrate that transcript profiling of NHPs could provide comparative genomic data to validate and better focus experimental animal models of human neurological disorders.