Aging and Mutation Load in Transgenic Medaka Fish

青鳉鱼（青鳉）转基因的大蓝突变检测系统是一个很好的模型，直接在体内分析的年龄和突变负荷（突变频率和模式），考虑相关的参数，如组织类型和某些环境条件，包括温度。该系统提供了一种新的模型，用于比较小鼠与非哺乳类脊椎动物中的诱变方面。中心假设是，突变过程，因为它涉及到老化是广泛的所有脊椎动物之间的相似，这意味着先前的观察自发突变频率和模式与老化的小鼠将观察到在非哺乳类脊椎动物，青。此外，青鳉鱼提供了一种新的脊椎动物衰老模型，与哺乳动物模型和流行的无脊椎动物衰老模型（C。elegans和D. melanogaster）。预计温度是鱼类寿命的主要决定因素。在衰老研究中使用鱼类模型的基本原理是，考虑到啮齿动物和人类之间更接近的进化关系，从鱼类到小鼠的自发突变的进化保守性可能可以外推到人类（即，鱼和老鼠之间的进化距离（约450兆年）大于老鼠和人类之间的进化距离（约65兆年））。该项目的目的是确定在三种不同温度下保持的幼鱼和老鱼的体细胞组织和生殖系中的突变负荷。预计这些发现将提供有关老年组织类型和温度突变负荷的初步数据。试点数据对于规划未来的实验将很重要。在此建议之前，不可能比较各种参数（即，年龄、组织类型和温度）影响远缘脊椎动物物种中的自发诱变。

Medaka fish (Oryzias latipes) transgenic for the Big Blue mutation detection system are an excellent model for direct in vivo analysis of age and mutation load (mutation frequency and pattern) with consideration of associated parameters such as tissue type and certain environmental conditions, including temperature. This system provides a novel model for comparison of aspects of mutagenesis in the mouse with those in a non-mammalian vertebrate. The central hypothesis is that the mutational process as it relates to aging is broadly similar among all vertebrates implying that previous observations made regarding spontaneous mutation frequency and pattern with aging in the mouse will be observed in a non-mammalian vertebrate, the medaka. In addition, medaka fish provide a new vertebrate model of aging with distinct differences from mammalian models and the popular invertebrate models of aging (C. elegans and D. melanogaster). It is expected that temperature is a major determinant of longevity in fish. The rationale for use of a fish model in aging research is that the evolutionary conservation of spontaneous mutations from fish to mouse can likely by extrapolated to humans given the closer evolutionary relationship between rodents and humans (i.e., the evolutionary distance between fish and mouse (about 450 megayears) is greater than mouse and human (about 65 megayears)). The objective for the project is to determine the mutations load in a somatic tissue and the germline in young and old fish maintained at three different temperatures. It is anticipated that the findings will provide preliminary data regarding mutation load in old age with tissue type and temperature. The pilot data will be important for planning future experiments. Prior to this proposal, it was not possible to compare the various parameters (i.e., age, tissue type and temperature) affecting spontaneous mutagenesis in distantly related vertebrate species.