“Gene Targeting in the Rat? Cut it out!”

Schematic overview of the development of rat genome manipulation strategies and targeted gene modifications in the rat germline. The timelines start in the early 1990s with the development of traditional transgenesis by pronuclear microinjection in zygotes. The majority of advances have been made in the last decade. Importantly, targeted-gene knockout rats have been recently produced by Geurts et al. via the ZFN technology (24). Homologous recombination-based gene replacement models, however, have not been produced. With the steady development of these technologies, HR-based gene replacement rat models are anticipated in the near future. ENU, n-ethyl-n-nitrosourea; RNAi, RNA interference; ZFN, Zinc-finger nucleases; SCNT, Somatic cell nuclear transfer; SSC, Spermatogonial stem cells; ES cells, Embryonic stem cells; iPS cells, induced Pluripotent stem cells; HR, Homologous recombination.