Fish as Genetic Models for Aging

秀丽线虫和黑腹果蝇等模型系统已被用于研究衰老的遗传学，发现了一些与衰老相关的重要基因。然而，这些无脊椎动物模型无法识别脊椎动物特有的长寿基因。我们建议使用鲤科鱼类Cynolebias，通常被称为一年生鱼，因为它的平均寿命为一年。然而，它作为遗传模型的实用性还没有被探索过。这项建议的目的是建立食蟹虫可以作为脊椎动物遗传模式生物用于衰老研究。为了实现这一目标，在第一个具体目标中，我们将确定辛诺比斯的寿命曲线。在第二个具体目标中，我们将建立遗传方法对食蟹的适用性。我们认为，斑马鱼的化学诱变、体外受精、二倍体、不同品系的鉴定和连锁标记的鉴定等试剂和遗传方法都可以适用于斑马鱼，因为这两种鱼都属于鲤科鱼类。这一建议的结果将为建立Cynolebias作为衰老研究的模型提供足够的背景数据。这些结果也将作为未来NIH R01拨款申请的初步数据，重点是筛选长寿命的细胞偏爱突变。

Model systems such as Caenorhabditis elegans and Drosophila melanogaster have been used to study genetics of aging, which identified some important genes, associated with aging. However, these invertebrate models cannot identify longevity genes that are unique to vertebrates. We propose to use Cynolebias, a cyprinid fish, commonly known as annual fish because it has an average life span of one year. However, its utility as a genetic model has not been explored. The goal of this proposal is to establish that Cynolebias could be used as a vertebrate genetic model organism for aging studies. To accomplish this goal, in the first specific aim, we will determine life-span curves for the Cynolebias. In the second specific aim, we will establish the applicability of genetic methods to Cynolebias. We propose that the reagents and genetic methods employed in zebrafish such as chemical mutagenesis, in vitro fertilization, diploidization, identification of different strains and identification of linkage markers, can be adapted to Cynolebias since both these fish belong to the cyprinid form of fishes. The results of this proposal will generate sufficient background data for establishing Cynolebias as a model for aging research. These results will also serve as preliminary data for a future NIH R01 grant application focusing on screening of Cynolebias mutants for long life span.