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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 项目1暴露在环境毒物中的发展后果 目的：1)鉴定脊椎动物发育过程中受砷干扰的基因；2)颌骨发育过程中受2，3，7，8-四氯二苯并-对二恶英(TCDD)干扰的基因。 结果：鉴定出了对低砷水平有反应的99个基因。19个聚集在一个与免疫反应和癌症显著相关的调控网络中。其他研究将有助于解释砷在发育过程中对免疫系统造成的干扰的后果。TCDDexposure to TCDD显著上调了对颌骨发育至关重要的叉头盒基因。该基因在TCDD介导的颌骨畸形中的作用将通过使用反义吗啉抑制其在斑马鱼中的表达来确定。 项目2狗鲨ABCB1-4基因座的基因组结构。 目的：ABC超家族是一个运输蛋白的大家族。ABCB1(B1)和ABCB4(B4)分别在多药耐药和胆盐解毒中起关键作用。该项目的目标是对含有B1的鲨鱼基因组基因进行测序，以确定是否存在第二个B家族基因。 结果：认为导致B1和B4基因的复制事件发生在哺乳动物与软骨鱼类分化后。然而，对现存的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。从文昌鱼基因组中提取的7条细菌人工染色体(BAC)进行了部分测序，生成了一个150kb的支架。这一分析应该确定该基因座内ABCB基因的数量，并提供对其调控的洞察。