Suppose I use "pBABE-puro-GFP-wt-GeneX" to get GeneX expressing with GFP (I am not sure whether it will replace the endogenous GeneX or get inserted somewhere else since the pBABE-puro vector uses retroviral integration, the integration site would be random throughout the genome, and not necessarily at the endogenous LMNA locus. Is this true?)

Now, if I use shRNA for GeneX under the U6 promoter and retrovirus-mediated transduction of these cells, would I get silencing of both the overexpression as well as the endogenous GeneX?

I doubt that the overexpressing gene would be too high, and plus, cells will push more overexpression of the gene, so we wouldn't be able to get it silenced.

Please suggest, if I am missing something here!

Reason of using this set up to easily make sure whether GeneX is silenced or not under microscope.