"Xenopus Microarrays: A Tool for Molecular Toxicology"

“非洲爪蟾微阵列：分子毒理学的工具”

• 批准号: 6690273
• 负责人: Hyesook Kim
• 金额: $ 42.22万
• 依托单位: DETROIT R & D, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-19 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6690273
• 关键词: Xenopus; environmental toxicology; gene expression; genetic regulation; hazardous substances; laboratory mouse; laboratory rat; method development; microarray technology; polymerase chain reaction

DESCRIPTION (provided by applicant): Each year, approximately 120,000 babies are born in the US with a major birth defect and genetic and environmental factors play an important role. Embryonic differentiation pathways are highly conserved among vertebrates. The Xenopus laevis embryo is an established toxicology model with ease of chemical exposure. Inter-laboratory studies demonstrated the reliability of the Frog Embryo Teratogenesis Assay-Xenopus (FETAX). Xenopus microarray analysis holds great promise as a versatile tool for drug screening and mechanistic studies of environmental toxicology. Our long-term goal is to develop Xenopus microarrays, categorize environmental toxicants according to their gene expression profiles and discover markers of environmental contaminants. About 18,500 EST clones were obtained from NIEHS. Initial studies completed in the Phase I with about1,200 clones demonstrate the feasibility of using Xenopus microarrays to identify genes responsive to phorbol 12-myristate 13-acetate (PMA) in early embryogenesis. In the Phase II, we will develop high-density cDNA microarrays and identify genes regulated by 7 classes of toxicants. These results will be utilized to produce diagnostic subarrays. We will also produce interspecies extrapolation chips to study conservation of gene regulation by toxicants. In addition, the feasibility of use of X. laevis chips for a X. tropicalis genetic manipulation study will be explored.

描述（由申请人提供）：每年，美国大约有 120,000 名患有严重先天缺陷的婴儿出生，遗传和环境因素起着重要作用。胚胎分化途径在脊椎动物中高度保守。非洲爪蟾胚胎是一种已建立的毒理学模型，易于接触化学物质。实验室间研究证明了青蛙胚胎致畸检测-非洲爪蟾 (FETAX) 的可靠性。非洲爪蟾微阵列分析作为药物筛选和环境毒理学机制研究的多功能工具具有广阔的前景。我们的长期目标是开发爪蟾微阵列，根据环境毒物的基因表达谱对其进行分类，并发现环境污染物的标记。从 NIEHS 获得了约 18,500 个 EST 克隆。第一阶段完成的初步研究涉及约 1,200 个克隆，证明了使用非洲爪蟾微阵列识别早期胚胎发生中对佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA) 敏感的基因的可行性。在第二阶段，我们将开发高密度cDNA微阵列并鉴定受7类毒物调控的基因。这些结果将用于产生诊断子阵列。我们还将生产种间外推芯片来研究有毒物质对基因调控的保护。此外，还将探讨利用 X. laevis 芯片进行热带 X. 基因操作研究的可行性。