ENHANCED DEVELOPMENT OF THE XIPHOPHORUS MODEL SYSTEM

描述（申请人提供）：剑鱼作为脊椎动物实验模型用于基础生物医学研究已有60多年的历史。该R24提案概述了资源和研究组成部分，旨在维护和加强剑鱼遗传资源中心（XGSC），该中心自20世纪30年代以来一直在美国运作，使其成为世界上最古老的活动物资源中心之一和国家科学宝藏。XGSC在1,400多个水族馆中拥有超过60个纯种遗传系，代表25种剑鱼。XGSC为代表11个国家的30多个实验室的研究人员提供了纯种鱼和材料。xiphohorus实验模型的传统优势包括对完整动物体内复杂表型相关的遗传模式进行无偏见评估。例如，肿瘤易感性的遗传控制已经在纯xiphohorus菌株和选择的种间杂交种中被记录下来，用于各种自发和诱导的肿瘤，包括几种遗传上不同的黑色素瘤。

DESCRIPTION (provided by applicant): Xiphophorus fishes have been used as a vertebrate experimental model for fundamental biomedical research for over 60 years. This R24 proposal outlines both resource and research components designed to maintain and enhance the Xiphophorus Genetic Stock Center (XGSC) that has operated within the United States since the 1930's making it one of the oldest live animal resources centers worldwide and a national scientific treasure. The XGSC houses over 60 pedigreed genetic lines representing 25 Xiphophorus species in over 1,400 aquaria. The XGSC has provided pedigreed fish and materials to researchers in over 30 laboratories representing 11 countries. The traditional strength of the Xiphophorus experimental model involves the non-biased assessment of genetic inheritance patterns associated with complex phenotypes within intact animals. For example, genetic control of tumor susceptibility has been documented in both pure Xiphophorus strains and select interspecies hybrids, for a variety of spontaneous and induced neoplasms including several genetically distinct melanomas. Our preliminary studies represent a first global comparison of the relative abundance of species-specific allele expression in two vertebrate species and Fl hybrids. In this initial study we were able to identify substantial changes in gene expression levels for parental alleles in the interspecies hybrid genetic background. We also found a new class of genetic interactions that lead to substantially suppressed gene expression in Fl hybrids relative to either parent. These initial experiments, employing RNAseq to follow allele specific gene expression in Fl interspecies hybrids, serve as examples of the Xiphophorus model may be used to uncover new knowledge regarding the mechanics of gene interactions, the genetic basis of developmental programs, complex behaviors, and the molecular processes underlying disease initiation and progression. If the goals of this proposal are realized, mechanistic dissection of Xiphophorus interspecies hybrid melanoma models may be approached and the results gleaned will have translational significance to tumorigenesis in humans.