The end of the past year included an outstanding experiment published on December 26, in Cell, from Austin Smith’s laboratory in Cambridge, UK.
Capture of authentic embryonic stem cells from rat blastocysts. Buehr M, Meek S, Blair K, Yang J, Ure J, Silva J, McLay R, Hall J, Ying QL, Smith A. Cell. 2008 Dec 26;135(7):1287-98.
Indeed, the group of Austin Smith, succeeded to obtain the first rat ES cells capable of colonising somatic and germ-line tissues, capable of forming chimeras, and capable of transmitting their genome to the progeny. The key of this achievement, in contrast to many previous attempts by various groups, has been the use of a combination of defined specific inhibitors (3i/2i) in the presence of LIF. Specially successful was the combination of 2i (inhibitors of the MEK and GSK3 pathways)+LIF. Even though the success rate is still rather low it lays the ground for future experiments in order to find the most adequate combinations of rat ES-cell donors and rat blastocysts for optimal results.
In 2003 we learnt about the cloning of rats by an experiment conducted in collaboration between Chinese and French scientists, commanded by Jean Paul Renard and first authored by Qi Zhou, awarded the TT Prize in Uppsala, at the TT2004 meeting (Zhou et al. Science 2003, Nov 14;302(5648):1179). It was envisaged this could be a way to overcome the limitation of a lack of rat ES cells for the production of specific rat knock-out strains. However, that experiment has proven very difficult to reproduce. Now, with this achievement by Austin Smith’s lab, and after eventually finding the optimal rat strain combinations and tissue culture conditions, it appears more feasible the possibility of preparing a variety of specific rat KOs.
In summary, a paper worth reading and discussing in laboratories and transgenic facilities. While reading this paper, it is particularly interesting how much they could learn from failure experiments and how they eventually came across a combination of factors that resulted in the generation of germ-line transmission capable rat ES cells.
Rat picture obtained from this WEB.