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New year seems like as good a time as any for another reminder: Be careful with your animal models! This edition brought to you by the Cre/Lox system. #methodsmatter 1/n
The Cre/Lox system is one of the most valuable & widely used tools in neuroscience (and other biological sciences) but like all models there are caveats. Location of transgene insertion for Tg-Cre lines carries the same risks of any Tg (namely disruption of endogenous genes) 2/n
This was excellently characterized by Goodwin et al. ( http://m.genome.cshlp.org/content/29/3/494.long). For instance the Tek-Cre mouse has 4 genes that are KO’d as result of disruption from Tg insertion (See Table 1). 3/n
Another issue is Cre going germline. Cre lines are only as valuable as they are specific (which is another topic entirely) but crucially just because Cre is driven by specific promoter doesn’t mean it remains that way after each generation. 4/n
In wonderful collaborative study from Luo et al., ( https://www.cell.com/neuron/fulltext/S0896-6273(20)30008-8) they characterized the frequency of Cre expression going germline in large number of commonly used CNS Cre lines 5/n
For instance in two different GFAP-Cre lines there was between 17-100% of offspring where Cre went germline. This is critical issue that can dramatically alter the interpretation of any study (it also appears to be sex dependent in some lines). 6/n
Overall just like any model #methodsmatter. Especially for complex breeding schemes it’s critical to be aware of the germline issue. If these aspects are controlled for the Cre/Lox system provides a valuable tool for dissecting complex biology. Happy Experimenting! 7/7
