Advancement of the Xiphophorus Model for Studying Disease

项目摘要 剑尾鱼作为长期存在的生物医学模型在多个领域进行翻译研究 纪律。它们被广泛应用于与多个NIH任务相关的研究课题中 机构/中心。剑尾鱼表现出其他动物模型所没有的几个特征， 包括高度的物种间遗传差异，产生物种间杂交的能力和 回交杂交种，代表人类疾病的适应性表型。最近完成的基因组 除了剑鱼模型的特点之外，几个剑鱼物种的组件还提供了 研究与疾病相关的复杂性状的遗传学无偏见评估的前提 人类。剑鱼遗传储备中心(XGSC)的主要目标是保持这些独特的 该模型的特点和保存该模型用于生物医学研究的优势。XGSC不仅是一个 拥有许多不同物种的资源中心，但也是唯一保存/保持高水平 易于处理的基因和表型多样性。XGSC保留了61个系谱系，分属于24个 剑鱼属物种。它驻留在德克萨斯州立大学，并积极服务于广泛的研究 自1993年以来一直是社区成员。XGSC具有广泛的国际影响力。我们提供纯种鱼和原料给 11个国家的30个实验室的研究人员。在此建议中，我们着眼于继续取得成功 经营，加强畜牧业，维护相关资源，并提供 为研究团体提供畜牧业培训，为主办机构提供学生培训。 拟议的剑鱼资源增强将利用与以下相关的疾病表型 癌症、代谢紊乱和人类疾病相关的分子表型。在创新方面，我们 将研究细胞、组织和器官水平，即癌症进展背后的遗传信号 和(B)代谢紊乱/肥胖。我们将通过描述这些过程中所涉及的细胞类型来实现这些目标 分子水平上的表型，这些表型在推动疾病进展方面起关键作用，并通过 破译疾病发展过程中的表观遗传变化。我们还将(C)描述等位基因 有助于代谢紊乱的形成。此外，我们会(D)扩大与疾病有关的资源。 剑鱼通过研究与各种人类疾病相关的分子特征，具有 主要目标是确定有助于疾病早期诊断和治疗的分子特征。这个 实现建议中目标的意义将是继续保持不可替代的支持 遗传资源和促进我们对分子、细胞和组织水平的理解 与人类健康和疾病相关的基因相互作用。提案的结果可以 推动我们对疾病病因的理解，导致新的治疗策略，并确定病因或 可在个体化药物中用作预测因子和靶点的调节等位基因。

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.