Experiments with conditional knockout mice are usually designed to compare knockout mice carrying floxed alleles and expressing the Cre enzyme under region specific promoter with counterparts carrying just the floxed allele as controls. But a situation where expression of Cre transgene itself affecting phenotype can confound results. Are mice with brain-specific Cre transgenes known to have distinct phenotypes?
Although it is possible (e.g. if the Cre transgene is 'blocking' the expression of another gene because of its insertion site) I personally never saw that. However, one thing I can think of is the strain. The strain of the mice can sometime strongly influences phenotype. Make sure your controls are of the same strain / same level of mixed background.
We agree with Jean-Nicolas in our lab, the strain is very important. Also, as Cre is huge and there is the potential for steric inhibition of various cellular processes, we breed to have Cre+/- and Lox +/+. We do not see specific issues in our Cre mice though, but we have never undertaken a specific study.
Here is a paper showing the phenotype in the midbrain of Wnt1::cre mice.
Dev Biol. 2013 Jul 15;379(2):229-34. doi: 10.1016/j.ydbio.2013.04.026. Epub 2013 May 3.
The widely used Wnt1-Cre transgene causes developmental phenotypes by ectopic activation of Wnt signaling.
Lewis AE, Vasudevan HN, O'Neill AK, Soriano P, Bush JO.
I think many people who have worked with cultures or other model systems would like to translate their findings to in-vivo conditions and Cre-loxp system is an obvious choice to consider. A review on the above topic would be very useful for early researchers in the area.
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