Development of novel rat models for site-specific transgene integration

The goal of this proposal is to develop novel rat strains that can be used to efficiently generate site-specific transgenic rat models via pronuclear microinjection. The laboratory rat (R. norvegicus) is a central experimental animal in several fields of biomedical research, such as cardiovascular diseases, aging, infectious diseases, autoimmunity, cancer models, transplantation biology, inflammation, cancer risk assessment, industrial toxicology, pharmacology, behavioral and addiction studies, and neurobiology. Up till recently, the ability of creating genetically modified rats has been limited compared to that in the mouse mainly due to lack of genetic manipulation tools and technologies in the rat. The isolation and establishment of rat embryonic stem (rES) cells by Drs. Ying and Smith's groups at the end of 2008 revolutionized the capability of making genetically modified rat models. As a result, rat transgenics is becoming as precise and powerful as has been the case in mice, yielding better models of