Hello,
Does anyone know whether activity of the enhancer-promoter CAG is affected by pathologic changes?
If I use the CAG promoter to drive GFP expression in the brain, I expect that both neurons and glia will express GFP. Would the disease state of the brain alter GFP expression thus induced by CAG? e.g., if a middle cerebral artery occlusion stroke model or an LPS challenge is administered to these animals, astrocytes become reactive and there is a change in the expression of many native astrocyte genes. Does anyone know whether the activity of CAG would be unchanged in such reactive astrocytes, or might it be enhanced or decreased?
I understand that the some viral promoters can become more active under stress, so just wanted to check what is known about CAG promoter activity in normal and diseased cells.
Thanks for your input!
Dear Anusha,
This is a poorly examined research field. A few studies claimed GFP expression can evoke diseases in CAG-GFP transgenic animals; so, probably, the increased GFP expression is the initial cause of the disease, not the consequence. GFP TG mice which were generated by other TG construct may also have diseases.
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Dear Nándor,
Thank you for these papers, they are illuminating indeed. I will have to watch out for this effect of GFP also.
However, my question is that if I induce a pathology in animals expressing a gene under CAG control, is the level of protein expressed (under CAG control) likely to be different after disease induction, possibly due to enhanced CAG promoter activity under inflammatory stress? I am unable to find any information on whether disease modifies CAG activity when used in an expression system like this.
Thanks,
Anusha
Besides pathological conditions, GFP expression under the control of the CAG promoter might change, but I also didn't find data regarding this issue. In my opinion, the reason of lacking these studies is simple: GFP is usually utilized as a "visibility" marker, so researchers don't like to admit their marker selection was wrong and its expression (fluorescence) changed in an unexpected way.
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