ZEBRAFISH AS A MODEL FOR BIOMEDICAL RESEARCH

斑马鱼作为生物医学研究的模型

• 批准号: 3421638
• 负责人: PERRY B. HACKETT
• 金额: $ 15.01万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3421638
• 关键词: Osteichthyes; alternatives to animals in research; antibody; antisense nucleic acid; biological models; developmental genetics; disease /disorder model; gel electrophoresis; gene expression; genetic library; genetic regulation; genetic regulatory element; genetic transcription; genetic translation; genetically modified animals; hormone receptor; in situ hybridization; messenger RNA; microinjections; model design /development; northern blottings; nucleic acid hybridization; nucleic acid probes; restriction mapping; ribozymes; site directed mutagenesis; southern blotting; thyroid hormone binding protein; thyroid hormones; triiodothyronine

The long term goal of this project is to develop zebrafish, Brachydanio rerio, as a high-connectivity-model vertebrate organism for biomedical research. Fish have several outstanding qualities for development as a high-connectivity model system for studies in developmental genetics and studies of diseases affecting genes that control growth that control growth and development in vertebrates. The attractive qualities of zebrafish include the following: 1) The zebrafish embryo can be easily examined as it develops in a transplant sac outside of its mother with very little care. 2) The fish egg can be easily manipulated to develop gynogenetically to yield homozygous offspring. 3) Fish are simpler vertebrates than mammals. 4) Effects of abnormal gene expression can be studied in transgenic fish which are easy to produce in large numbers at low cost. 5) Zebrafish eggs can be produced in relatively large numbers on almost a daily basis; the eggs are transparent and easy to microinject. 6) Zebrafish mature in about 4 months, thus facilitating genetic analysis of offspring at the same rate as in mice. To demonstrate the power of using zebrafish as a model system, regulation of the thyroid hormone receptor (c-erbA) gene(s) of zebrafish will be investigated and characterized. Regulation of c-erbA gene expression its critical in normal development in all vertebrates, including humans. Investigations into the complex interactions of c-erbA in the normal physiology of mammalian development may be greatly assisted by a simpler vertebrate system that permits examination of c-erbA expression during early development that is obscured in mammals. Moreover, since fish are not warm-blooded, the role of c-erbA in thermogenesis may be avoided in this organism thereby simplifying analyses. Early embryonic development is well studied in zebrafish, giving us a solid foundation on which to base our investigation. The goals are designed to 1) to examine the c-erbA gene family of fish in order to help clarify the roles the product of this gene plays in vertebrate development, and 2) to investigate the effects of abnormal expression of c-erbA that might be applicable to both thyroid disease and to oncogenesis.

该项目的长期目标是培育斑马鱼、Brachydanio rerio，作为生物医学的高连接模型脊椎动物 研究。 鱼类作为生物体具有多种可供发育的优秀品质 用于发育遗传学研究的高连接模型系统 影响控制生长基因的疾病研究 和脊椎动物的发育。 斑马鱼的迷人品质 包括以下内容： 1）斑马鱼胚胎可以很容易地检查，因为它 在很少照顾的情况下，在其母体外的移植囊中发育。 2) 鱼卵可以很容易地进行雌核发育 产生纯合后代。 3）鱼类是比哺乳动物更简单的脊椎动物。 4) 可以在转基因鱼中研究异常基因表达的影响 易于以低成本大量生产。 5）斑马鱼卵 几乎每天都可以大量生产；这 鸡蛋是透明的，易于显微注射。 6) 斑马鱼大约成熟 4个月，从而有利于以相同的速度对后代进行遗传分析 就像老鼠一样。 为了展示使用斑马鱼作为模型系统的力量， 斑马鱼甲状腺激素受体 (c-erbA) 基因的调控 将进行调查和表征。 c-erbA基因的调控 表达对所有脊椎动物的正常发育至关重要，包括 人类。 c-erbA 复杂相互作用的研究 哺乳动物发育的正常生理学可能会受到以下因素的极大帮助： 允许检查 c-erbA 表达的更简单的脊椎动物系统 在哺乳动物的早期发育过程中，这一点被掩盖了。 而且，由于鱼 不是温血动物，c-erbA 在生热作用中的作用可以在 这种生物体从而简化了分析。 早期胚胎发育是 在斑马鱼中进行了深入研究，为我们奠定了坚实的基础 我们的调查。 目标旨在 1) 检查 c-erbA 基因 鱼类家族，以帮助阐明该基因产物的作用 在脊椎动物发育中发挥作用，2）研究 c-erbA 的异常表达可能适用于甲状腺 疾病和肿瘤发生。