Genome editing pig models with elements for controllable gene expression

Abstract

Conditional gene regulation systems can control gene expression in predefined tissues or organs at a desired time. Site-specific recombinase systems and chemically induced gene expression systems are the two most widely used approaches for creating genetically modified (GM) animals with conditional regulation of gene expression. Generation of GM pigs with controllable elements, usually involving multiple gene editing, used to be a major challenge due to a lack of germ line-competent pluripotent stem cells. With the emergence of artificial endonuclease-mediated gene editors, a variety of GM pigs with recombinase-specific recognition elements or chemically induced elements for conditional regulation of gene expression have been generated by the combination of site-directed knock-in of somatic cells and somatic cell nuclear transfer technology, allowing conditional deletion of endogenous genes or overexpression of exogenous genes in pigs. These inducible tool pig models will greatly facilitate the production of GM pigs and broaden the applications of transgenic pigs in biomedicine and agriculture fields. In this paper, we review the progress in the construction and application of pigs with controllable elements using gene editing techniques.