Drug Discovery
only for research models but also for the creation of GEMs. Combined with its versatility and multi- ple applications, the B6 is now preferred for most GEM projects.
One particular B6 substrain, C57BL/6NTac, was chosen by international consortia to be the source of embryonic stem (ES) cells used for all new GEMs. As a result, more than 22,000 mouse knockout lines have been created on this C57BL/6NTac background. In contrast to older techniques, which relied on other, less-useful mouse strains, the ability to generate GEMs directly on a B6 background accelerates timelines and increases research possibilities. Together with CRISPR gene editing techniques, B6 ES cells make it possible to generate research models with ever increasingly complex genetic alterations, such as mice-possessing humanised genes for test- ing biologics.
This rich resource of GEMs on a defined back- ground is reshaping what is possible for researchers, by allowing them to understand how specific genes contribute to numerous disease pro- cesses and to identify novel therapeutic targets. The fact that all these mice are on the B6 back- ground is important for several reasons. First, it
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enables direct comparisons between different GEMs since only the engineered genes differ between these mice and wildtype B6 controls. Second, since their genetic background is the same, this makes it possible to perform complex experiments involving genetic crosses and/or cell/tissue transplants between different GEMs. Finally, and perhaps most importantly, a GEM on a B6 background can be used in all the same diverse experimental models as wildtype B6 mice. Of course, there are several caveats to these approaches, most importantly that the genetic background of the GEMs in question are on a defined B6 substrain with equivalent microbiomes to exclude the confounding effects of these vari- ables, as discussed earlier. Nevertheless, this tool- box of B6 GEMs, along with the B6’s research ver- satility, combine to provide a powerful platform for research and discovery.
Advanced applications for B6 mice The obese B6
B6 mice, especially B6N substrains, are exception- ally prone to developing obesity, insulin resistance and diabetes when fed a high-fat diet. This makes the obese B6 useful in identifying therapeutic
Drug Discovery World Fall 2017
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