Pickart Michael A, Sivasubbu Sridhar, Nielsen Aubrey L, Shriram Sabitha, King Richard A, Ekker Stephen C
Department of Oral Sciences and Minnesota Craniofacial Research Training Program (MinnCResT), University of Minnesota, Minneapolis, MN, USA.
Pigment Cell Res. 2004 Oct;17(5):461-70. doi: 10.1111/j.1600-0749.2004.00189.x.
Genetic model organisms are increasingly valuable in the post-genomics era to provide a basis for comparative analysis of the human genome. For higher order processes of vertebrate pigment cell biology and development, the mouse has historically been the model of choice. A complementary organism, the zebrafish (Danio rerio), shares many of the signaling and biological processes of vertebrates, e.g. neural crest development. The zebrafish has a number of characteristics that make it an especially valuable model for the study of pigment cell biology and disease. Large-scale genetic screens have identified a collection of pigmentation mutants that have already made valuable contributions to pigment research. An increasing repertoire of genomic resources such as an expressed sequence tag-based Gene Index (The Institute for Genomic Research) and improving methods of mutagenesis, transgenesis, and gene targeting make zebrafish a particularly attractive model. Morpholino phosphorodiamidate oligonucleotide (MO) 'knockdown' of pigment gene expression provides a non-conventional antisense tool for the analysis of genes involved in pigment cell biology and disease. In addition, an ongoing, reverse-genetic, MO-based screen for the rapid identification of gene function promises to be a valuable complement to other high-throughput microarray and proteomic approaches for understanding pigment cell biology. Novel reagents for zebrafish transgenesis, such as the Sleeping Beauty transposon system, continue to improve the capacity for genetic analysis in this system and ensure that the zebrafish will be a valuable genetic model for understanding a variety of biological processes and human diseases for years to come.
在基因组学时代之后,遗传模式生物对于提供人类基因组比较分析的基础变得越来越有价值。对于脊椎动物色素细胞生物学和发育的高阶过程,小鼠一直是历史上的首选模型。一种互补的生物,斑马鱼(Danio rerio),具有许多脊椎动物的信号传导和生物学过程,例如神经嵴发育。斑马鱼具有许多特性,使其成为研究色素细胞生物学和疾病的特别有价值的模型。大规模遗传筛选已经鉴定出一系列色素沉着突变体,这些突变体已经对色素研究做出了有价值的贡献。越来越多的基因组资源,如基于表达序列标签的基因索引(基因组研究所)以及不断改进的诱变、转基因和基因靶向方法,使斑马鱼成为一个特别有吸引力的模型。吗啉代磷酰胺二聚体寡核苷酸(MO)对色素基因表达的“敲低”为分析参与色素细胞生物学和疾病的基因提供了一种非常规的反义工具。此外,正在进行的基于MO的反向遗传学筛选以快速鉴定基因功能,有望成为理解色素细胞生物学的其他高通量微阵列和蛋白质组学方法的有价值补充。用于斑马鱼转基因的新型试剂,如睡美人转座子系统,继续提高该系统中的遗传分析能力,并确保斑马鱼在未来几年将成为理解各种生物学过程和人类疾病的有价值的遗传模型。