Gene targeting: There is always a debate on gene integration in to the host animal.
It is random gene integration Vs gene targeting. Perhaps most significantly, pro-nuclear injection cannot be used to modify the animals' own genes. By contrast, target modifications to endogenous genes have been achieved earlier in mouse model and now in farm animals also. When introduced into the early embryo these cells contribute to the germline. They can also undergo homologous recombination with transfected foreign DNA so that precise, targeted changes can be introduced. The combination of these two properties means that gene targeting of the mouse germline is now routine, allowing for the deletion, replacement or modification of selected genes. Recombination on either side of the marker gene results in its precise insertion into the chromosome at the same time and delete some or the entire target gene. Precise targeting events are very rare (perhaps 1 in 106 cells) and, therefore special methods must be taken for identifying and selecting the correctly targeted cells.