ENVIRONMENTAL TOXICANT PERTURBATION OF ZEBRAFISH GENE EXPRESSION & DEVELOPMENT

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 项目#1暴露于环境毒物的发育后果 目的：1）鉴定a）脊椎动物发育过程中受砷干扰的基因;和B）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：砷研究人员发现了99个对低砷水平有反应的基因。其中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。进一步的研究将有助于解释砷介导的干扰免疫系统在发展过程中的后果。TCDD暴露于TCDD显着上调叉头盒基因颌骨发育的关键。该基因在TCDC介导的颌骨畸形中的作用将通过使用斑马鱼中的反义吗啡来敲除其表达来确定。 项目#2角鲨ABCB 1 -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。ABCB 1（B1）和ABCB 4（B4）分别在多药耐药性和胆盐解毒中至关重要。该项目的目标是对携带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：B1和B4的复制事件可能发生在哺乳动物与软骨鱼类分化之后。然而，现存的非哺乳类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。对来自角鲨基因组的7条细菌人工染色体（BAC）进行部分测序，以产生150 kb的支架。这种分析应该确定基因座内ABCB基因的数量，并提供对它们的调控的了解。

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.