Marvanová Markéta, Ménager Jean, Bezard Erwan, Bontrop Ronald E, Pradier Laurent, Wong Garry
Functional Genomics and Bioinformatics Laboratory, Department of Neurobiology, A. I. Virtanen Institute, University of Kuopio, 70211 Kuopio, Finland.
FASEB J. 2003 May;17(8):929-31. doi: 10.1096/fj.02-0681fje. Epub 2003 Mar 5.
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 up-regulated, 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.
由于非人灵长类动物（NHPs）具有相似的生理特征，它们已为许多人类相关疾病提供了可靠的实验动物模型。尽管如此，在诸如艾滋病和阿尔茨海默病等重要疾病的发病、进展和结果方面仍存在显著差异，其潜在原因尚不清楚。我们探索了人类高密度寡核苷酸阵列用于检测NHPs基因组转录谱的效用。将来自人类（智人）、普通黑猩猩（黑猩猩属）、食蟹猴（猕猴属）和普通狨猴（狨属）前额叶皮质的总RNA进行标记，并与Affymetrix U95A基因芯片探针阵列杂交。为了进行比较，添加了先前从普通黑猩猩和猩猩（红毛猩猩属）获得的相应数据。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疾病有关的基因在NHPs中存在并受到调控。猕猴和狨猴中不存在一种参与多巴胺代谢的基因（儿茶酚-O-甲基转移酶）。与人类相比，NHPs中谷氨酸受体2上调，而转录相关基因下调。我们证明，NHPs的转录谱分析可以提供比较基因组数据，以验证和更好地聚焦人类神经疾病的实验动物模型。
