Gene Targeting in Embryonic Stem Cells, I: History and Methodology

There have been extensive studies with embryonic stem cells from the mouse embryo, and these studies have led directly to a greater understanding of human genetic diseases, gene interactions, embryo development, and organogenesis both in vivo and in vitro. Pluripotential stem cells of the mouse can be classified into four major groups: embryonal carcinoma cells (ECCs), embryonic stem cells (ESCs), primordial germ cells (PGCs), and induced pluripotent stem cells (iPSCs). Various types of stem cells can be maintained in an undifferentiated state for many passages in appropriate culture conditions while retaining the pluripotency that makes them so valuable. It is this ability to grow in culture in large numbers that makes them useful for the introduction of gene alterations, for the screening of very rare homologous recombination events that result in the precise, preplanned alteration, and finally for producing animal models with designed mutations of diverse types.