Color-coded transposor-mediated rat mutagenesis

描述(由申请人提供)： 大鼠是研究哺乳动物生物学的重要实验动物。这些啮齿动物对生理、神经行为、器官移植和毒理学研究特别有用。此外，现在还可以为大鼠提供特殊的遗传和基因组资源，包括用当前组装和注释对基因组进行测序，预测23,400个基因(www.ensembl.org/rattus_norvejcus)和50,000多个表达序列标签(EST)。大鼠模型系统现在为功能基因组研究做好了准备。然而，促进大鼠系统中严重缺乏的基因功能研究的一个特别有价值的资源是大量突变和持续不断的新突变来源。尽管常规地产生表达外源基因的转基因大鼠是可能的，但对于这种物种来说，没有胚胎干细胞可以用于产生小鼠常规的靶向突变。容易地产生新的突变大鼠品系的能力将极大地促进这种中央实验室动物用于生物医学研究。这项建议的主要目标是通过转基因大鼠产生一个睡美人转座子突变系统，作为研究界免费获得的资源，以便容易地在大鼠身上产生和分子鉴定新的突变。

DESCRIPTION (provided by applicant): Rats are very important laboratory animals for studying mammalian biology. These rodents are especially useful for physiological, neurobehavioral, organ transplantation, and toxicological studies. In addition, exceptional genetic and genomic resources are now available for the rat, including a genome that has been sequenced with a current assembly and annotation predicting 23,400 genes (www.ensembl.org/Rattus_norvegjcus) and more than 50,000 expressed sequence tags (ESTs). The rat model system is now primed for functional genomic studies. However, one particularly valuable resource to facilitate studies of gene function that is sorely lacking in the rat system is a large collection of mutants and a continuous source of new mutations. Although it is possible to routinely generate transgenic rats to express exogenous genes, there are no embryonic stem (ES) cells for this species that could be used to generate targeted mutations that is routine in the mouse. The ability to easily generate new mutant rat strains would significantly advance the use of this central laboratory animal for biomedical research. The primary objective of this proposal is to generate a Sleeping Beauty transposon mutagenesis system through transgenic rats to serve as a freely available resource to the research community to easily generate and molecularly identify new mutations in rats.