While knocking out a gene from the mice, some un-calculated stressed must have been developed in the mice (for sure) due to the process of knock out. In that situation, how much it is honest and justified conclusion that all the changes in mice phenotype is ONLY due to the gene knock out but not because of the process of knock out? If the process of knock out also leaves an impact on the resulting mice, than what should be the proper control? Whether any other gene could be knocked out (as we use house keeping gene in Real time PCR) for control?Thanks in anticipation.