ENVIRONMENTAL TOXICANT PERTURBATION OF ZEBRAFISH GENE EXPRESSION & DEVELOPMENT

斑马鱼基因表达的环境毒性扰动

• 批准号: 7960062
• 负责人: Antonio J. Planchart
• 金额: $ 7.91万
• 依托单位: MOUNT DESERT ISLAND BIOLOGICAL LAB
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-23 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960062
• 关键词: ABCB1 gene; Arsenic; Bacterial Artificial Chromosomes; Boxing; Carrier Proteins; Chondrichthyes; Computer Retrieval of Information on Scientific Projects Database; Development; Dioxins; Drug Metabolic Detoxication; Dysmorphology; Event; Exposure to; Family; Funding; Gene Expression; Gene Family; Genes; Genome; Genomics; Goals; Grant; Immune response; Immune system; Institution; Jaw; Maine; Malignant Neoplasms; Mammals; Mediating; Multi-Drug Resistance; Regulation; Research; Research Personnel; Resources; Role; Sequence Analysis; Shark; Source; Squalidae; Squalus acanthias; Structure; Tetrachlorodibenzodioxin; Toxic Environmental Substances; United States National Institutes of Health; Vertebrates; Zebrafish; bile salts; comparative; functional genomics; insight; knock-down; scaffold

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Project #1 Developmental Consequences of exposure to environmental toxicants Objectives: 1) To identify genes a) perturbed by arsenic during vertebrate development; and b) perturbed by 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) during jaw development. Results: Arsenic99 genes that respond to low arsenic levels were identified. Nineteen clustered in a regulatory network that is significantly associated with immune response and cancer. Additional studies will help explain the consequences of arsenic-mediated perturbation of the immune system during development. TCDDExposure to TCDD significantly upregulated a Forkhead box gene critical for jaw development. The role of this gene in TCDD-mediated jaw dysmorphology will be determined by knocking down its expression using antisense morpholinos in zebrafish. Project #2 Genomic structure of the ABCB1-4 locus of the Dogfish shark. Objectives: The ABC superfamily is a large family of transport proteins. ABCB1 (B1) and ABCB4 (B4) are critical in multidrug resistance and bile salt detoxification, respectively. The goal of this project is to sequence the shark genomic locus harboring B1 in order to determine if a second B-family gene exists. Results: It has been proposed that the duplication event leading to B1 and B4 occurred in mammals after their divergence from cartilaginous fish. However, genomic sequence analysis of extant non-mammalian vertebrates indicates the duplication event may have occurred earlier. Seven bacterial artificial chromosomes (BAC) from the Squalus acanthias genome were partially sequenced to generate a 150kb scaffold. This analysis should determine the number of ABCB genes within the locus and provide insight into their regulation.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 项目#1 暴露于环境毒物的发育后果 目标： 1) 鉴定 a) 在脊椎动物发育过程中受砷干扰的基因； b) 在下颌发育过程中受到 2,3,7,8-四氯二苯并-对二恶英 (TCDD) 的干扰。 结果：鉴定出了对低砷水平有反应的 99 个砷基因。十九个聚集在与免疫反应和癌症显着相关的监管网络中。其他研究将有助于解释发育过程中砷介导的免疫系统扰动的后果。 TCDD 暴露于 TCDD 显着上调了对下颌发育至关重要的 Forkhead box 基因。该基因在 TCDD 介导的颌畸形中的作用将通过使用反义吗啉在斑马鱼中敲低其表达来确定。 项目#2 角鲨 ABCB1-4 基因座的基因组结构。 目的：ABC 超家族是转运蛋白的一个大家族。 ABCB1 (B1) 和 ABCB4 (B4) 分别在多重耐药性和胆汁盐解毒中至关重要。该项目的目标是对含有 B1 的鲨鱼基因组位点进行测序，以确定是否存在第二个 B 家族基因。 结果：有人提出，导致 B1 和 B4 的重复事件发生在哺乳动物与软骨鱼分化后。然而，对现存非哺乳动物脊椎动物的基因组序列分析表明，复制事件可能发生得更早。来自 Squalus acanthias 基因组的 7 个细菌人工染色体 (BAC) 被部分测序，以生成 150kb 的支架。该分析应确定该位点内 ABCB 基因的数量并提供对其调控的深入了解。