"Germline transmission": how many time have mouse geneticists prayed to the Gods to decipher this magical message from their Southern blots and PCRs when trying to generate a knockout line?

Hopefully the recent technology (the "VelociMouse method") developed by Regeneron Pharmaceuticals will definitively overcome this hurdle (Poueymirou et al, 2007): by disrupting the zona pellucida with help of a laser, ES cells could be injected into 8-cell stage embryos, resulting in F0 generation founder mice entirely derived from the ES cells, thus directly amenable to phenotypic analysis and breeding.

Together with the large-scale gene targeting in ES cells (Valenzuela et al, 2003, Auwerx et al, 2004, Austin et al, 2004,Grimm, 2006), this technological advance may well represent a major step towards a high-throughput functional genomics of a mammalian species.