Advancement of the Xiphophorus Model for Studying Disease

研究疾病的剑尾动物模型的进展

• 批准号: 10270313
• 负责人: Caitlin Gabor
• 金额: $ 62.84万
• 依托单位: TEXAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10270313
• 关键词: Access to Information; Affect; Alleles; Animal Housing; Animal Husbandry; Animal Model; Animals; Area; Automobile Driving; Backcrossings; Behavior; Biological; Biological Models; Biology; Biomedical Research; Cancer Etiology; Cells; Chromosomes; Chronobiology; Communities; Complex; Consult; Country; Data; Development; Diagnosis; Discipline; Disease; Disease Progression; Disease model; Distant; Embryology; Endocrinology; Ensure; Epigenetic Process; Etiology; Exhibits; Experimental Models; Fishes; Fresh Water; Future; Gene Expression; Genes; Genetic; Genetic Drift; Genetic Epistasis; Genetic Variation; Genome; Genomics; Genotype; Goals; Health; Histocompatibility; Human; Hybrids; Immunology; Improve Access; Inbreeding; Institution; International; Knowledge; Laboratories; Lead; Malignant Neoplasms; Metabolic Diseases; Mission; Modeling; Molecular; Obesity; Optics; Organ; Organism; Orthologous Gene; Outcome; Parasitology; Phenotype; Physiology; Play; Population; Positioning Attribute; Procedures; Production; Publications; Publishing; Quantitative Trait Loci; Regulation; Research; Research Personnel; Research Training; Resources; Role; Selection for Treatments; Services; Signal Transduction; Study models; System; Texas; Tissues; Toxicology; Training; Translational Research; United States National Institutes of Health; Universities; Variant; Xiphophorus; animal resource; bioinformatics tool; cell type; disease diagnosis; disease phenotype; functional genomics; gene interaction; genetic pedigree; genetic resource; genetic variant; genomic locus; human disease; human model; improved; innovation; medical specialties; model development; molecular phenotype; novel; novel therapeutic intervention; nutrition; obesity development; operation; personalized medicine; preservation; student training; therapeutic development; trait; transcriptomics; translational model; tumor progression; tumorigenesis

Project Summary Xiphophorus fishes serve as long-standing biomedical models for translational research in multiple disciplines. They are used widely in research topics that connect to the missions of multiple NIH Institutions/Centers. Xiphophorus fish exhibit several features that no other animal model shares, including high level of inter-species genetic divergence, capability of producing inter-species hybrids and backcross hybrids, adaptive phenotypes representing human diseases. Recently accomplished genome assemblies for several Xiphophorus species, in addition to the specialties of Xiphophorus model, provide the premise to study non-biased assessment of genetics underlying complex traits associated with diseases in humans. The primary goal of the Xiphophorus Genetic Stock Center (XGSC) is to maintain these unique features and preserve the strength of this model to be used in biomedical research. The XGSC is not only a resource center hosting many different species, but also the only center that preserves/maintains high level of tractable genotypic and phenotypic diversity. The XGSC maintains 61 pedigreed lines that belong to 24 Xiphophorus species. It resides at Texas State University and has actively served a broad research community since 1993. XGSC has a wide international impact. We provide pedigreed fish and material to investigators in 30 laboratories of 11 countries. Herein this proposal, we focus on continuing successful operation of the XGSC, enhancing animal husbandry, maintaining relevant resources, and providing animal husbandry training for the research community, and student training for the host institution. Proposed enhancement of Xiphophorus resources will leverage the disease-like phenotypes related to cancer, metabolic disorders and the human disease-associated molecular phenotypes. Innovatively, we will investigate on the cellular, tissue and organ level, the genetic signaling underlying (a) cancer progression and (b) metabolic disorder/obesity. We will achieve theses goal by characterizing cell types involved in these phenotypes on the molecular level which are critically involved in driving disease progression and by deciphering epigenetic alterations during disease development. We will also (c) characterize alleles that contribute to metabolic disorder formation. In addition, we will (d) expand disease related resources of Xiphophorus by studying molecular traits that are associated with various types of human diseases, with a primary goal of identifying molecular traits that can benefit early disease diagnosis and treatment. The significance of achieving the goals in the proposal will be the support to continue to maintain irreplaceable genetic resources and advancing our understanding on the molecular, cellular and organismic level of genetic interactions associated with human health and diseases. The outcomes of the proposal can forward our understanding of disease etiology, lead to novel therapeutic strategies, and identify causal or regulatory alleles that may be utilized as predictors and targets in personalized medicine.

项目概要 剑尾鱼长期以来一直是多种领域转化研究的生物医学模型 学科。它们广泛应用于与多个 NIH 的任务相关的研究主题 机构/中心。剑尾鱼表现出其他动物模型所不具备的几个特征， 包括高水平的种间遗传分化、产生种间杂交的能力以及 回交杂交，代表人类疾病的适应性表型。最近完成的基因组 除了剑尾鱼模型的特殊性之外，还提供了几种剑尾鱼物种的组件 研究与疾病相关的复杂性状的遗传学的无偏见评估的前提 人类。剑尾鱼遗传资源中心 (XGSC) 的主要目标是保持这些独特的 特征并保留该模型在生物医学研究中使用的强度。 XGSC不仅是一个 拥有许多不同物种的资源中心，也是唯一一个保存/维持高水平物种的中心 易于处理的基因型和表型多样性。 XGSC 拥有 61 个纯种系，分别属于 24 个 剑尾属物种。它位于德克萨斯州立大学，并积极服务于广泛的研究 自 1993 年以来，XGSC 已成为社区成员。XGSC 具有广泛的国际影响力。我们提供纯种鱼和材料 11个国家30个实验室的研究人员。在此建议中，我们重点关注持续成功 XGSC 的运营，加强畜牧业，维护相关资源，并提供 为研究界提供畜牧业培训，为主办机构提供学生培训。 拟议的剑尾鱼资源增强将利用与剑尾鱼相关的疾病样表型 癌症、代谢紊乱和人类疾病相关的分子表型。创新地，我们 将在细胞、组织和器官水平上研究 (a) 癌症进展的遗传信号 (b) 代谢紊乱/肥胖。我们将通过表征这些涉及的细胞类型来实现这些目标 分子水平上的表型对于驱动疾病进展至关重要 破译疾病发展过程中的表观遗传变化。我们还将 (c) 表征等位基因 有助于代谢紊乱的形成。此外，我们将 (d) 扩大与疾病相关的资源 剑鱼通过研究与各种人类疾病相关的分子特征， 主要目标是识别有利于早期疾病诊断和治疗的分子特征。这 实现提案中目标的意义将是继续保持不可替代的支持 遗传资源并增进我们对遗传资源的分子、细胞和有机体水平的理解 与人类健康和疾病相关的遗传相互作用。提案的结果可以 增进我们对疾病病因学的理解，制定新的治疗策略，并确定因果关系或 可用作个性化医疗中的预测因子和靶标的调节等位基因。