Gene targeting in zebrafish: building models to assay disease genes

斑马鱼的基因打靶：建立模型来检测疾病基因

• 批准号: 8684468
• 负责人: DAVID J. GRUNWALD
• 金额: $ 22.35万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8684468
• 关键词: Address; Alleles; Behavior; Benign; Biological Assay; Biological Models; Cardiac; Cells; Development; Diagnosis; Disease; Embryo; Embryonic Development; Environment; Evaluation; Excision; Fishes; Gene Targeting; Genes; Genetic Predisposition to Disease; Genetic Recombination; Goals; Healthcare; Human; Human Activities; Human Genome; Ion Channel Protein; Knock-in Mouse; Knock-out; Laboratories; Lead; Long QT Syndrome; Measures; Mediating; Methods; Modeling; Pathogenicity; Patients; Pharmaceutical Preparations; Physiological; Physiology; Process; Proteins; Relative (related person); Reporter; Research Personnel; Research Subjects; Risk; Signal Transduction; Site; Stratification; System; Tamoxifen; Technology; Testing; Universities; Utah; Validation; Variant; Zebrafish; body system; design; genome sequencing; homologous recombination; human disease; interest; loss of function; new technology; novel; promoter; public health relevance; rapid technique; recombinase; screening; tool; transcription termination

DESCRIPTION (provided by applicant): The purpose of this proposal is to advance use of the zebrafish as an applied tool for helping to diagnose and develop treatments for human disease. This proposal aims to develop and test a new method for using the zebrafish to measure the relative activity and potential pathogenicity of allelic forms of human genes. Methods will be developed that allow the removal of specific zebrafish genes on demand and the expression of human genes in the zebrafish. As a test case, this proposal uses the new methods to determine if the zebrafish can be used to distinguish between normal and disease-causing forms of the KCNH2 gene, a gene that when defective leads to Long QT Syndrome.

描述（由申请人提供）：该提案的目的是促进斑马鱼作为一种应用工具的使用，以帮助诊断和开发人类疾病的治疗方法。该提案旨在开发和测试一种使用斑马鱼测量人类基因等位基因形式的相对活性和潜在致病性的新方法。将开发允许按需去除特定斑马鱼基因并在斑马鱼中表达人类基因的方法。作为一个测试案例，该提案使用新方法来确定斑马鱼是否可用于区分 KCNH2 基因的正常形式和致病形式，该基因有缺陷时会导致长 QT 综合征。