Knockout and knockdown of gene?

Question

Out of curiosity, I got this question whether knocking out (deletion) of a gene on one side and knocking down (RNAi) of the same gene on the other side will affect the cell in a similar manner or not.If not why?If yes, is it applied to every gene?**Knock out** of a gene will correspond to no expression (gene deletion) in the cell, which can be appropriate to confirm the functional specificity, to observe processes which are affected in its absence and some other processes which are compensating the absence of the gene.**Knockdown** of a gene will result in expression defect by decreasing the level of the transcript (mRNA silencing).Now, the points which I am wondering upon are:1. no mRNA presence and silenced mRNA will create two different environments for the cell to deal with or not.2. whether the whole amount of transcript should be targeted to have the same phenotype as of gene knockout.

Answer 1

Not really affect the cell in same manner but then theory is different than practice and the organism/animal model used also determines the phenotype of even KO and KD. KO usually we would expect to see no protein being formed of the gene in question, and thus we should be able to have the expected phenotype. For e.g. i made knock out mouse for Fanconi Anemia C and FA A gene. Theoretically i should have a great phenotype in both. My Fancc -/- had the same phenotype as humans and i was able to use for gene therapy treatments. Fanca-/- did not show any difference. So to answer your question, point is, when you make a construct and KO the gene, we are trying to eliminate ALL expression of the protein. In KD we are trying to lower the expression of the protein, now this lowering may or may not give you the answer you are seeking.

1. No mRNA presence and silenced mRNA will create two different environments for the cell to deal with. Yes. Once again depends on the organism you will use e.g. S. cerevisiae, C. elegans or mouse etc. Every KO is not lethal either.
2. I don't understand your point #2, same phenotype as KO? in a KD?

In summary, both processes would give you different answers but together that might be able to answer the questions you are seeking regarding the function of gene. Let me know i would be happy to discuss it further if you want. thanks