Our transgenic mice show a really strong phenotype which differs a lot from results of another group working with the same transgene. As our mice are on a pure C57Bl6J background and theirs was on a "mixed background" (we weren't given the exact mixture), I was wondering if it might be of interest to cross our cre mice on a mixed background too (e.g. with 129S1).
Does anyone have experience with the influence of mixed/pure background on cre expression?
I'm grateful for every hint on how to reduce cre expression through breeding in order to increase lifespan and observation time for our mice. Many thanks in advance!
I wonder if this could be due to the genomic location of Cre being different between your Cre line and your collaborator's? When knock-in mice are created by random insertion of the transgene, the level and pattern of transgene expression (and hence the phenotype) is dependent on the genomic context where the transgene lands. If your collaborators are using a Cre line with a random Cre insertion (which I think is more common with mixed/outbred backgrounds) and your lab has a Cre driver line which has known stable and high performance (eg Rosa26-Cre) this could mean your mice have a lot more Cre, are deleting your floxed cassette more ubiquitously, and therefore have a stronger phenotype. Getting a transgene onto a pure background is a lot of work and a lot of generations, so people only tend to do it for 'good' lines, and that might be what's happening here.
Any extra info about the mice or the transgene (eg, if the insertion location and copy number are known or not) might help us figure this out :) Sorry I can't answer the direct question you asked because I've never used mixed background animals myself to know if there's a difference.
Thanks for your answers so far! It is in fact the exact same cre mouse (originally purchased from the same breeders) but the other group seems to use a mixed background while we backcrossed it further with Bl6 mice (as they are the "standard" in our lab). So the insertion should not matter but only the background itself. As they are not our collaborators, unfortunately, they won't let us know more about their exact background. So I was just wondering if there is in fact a big influence of the background on cre expression. Just to see if it's worth trying to mix our background.