I don't have a lot of experience in the design of animal experiments.
Let's say factor X that is required in humans for the generation of long-lived plasma cells.
This is a completely theoretical questions, so I cannot provide you with information about factor X. I just want to know what I should theoretically.
I generate a mouse model and delete factor X, but 6 months old, non-immunized mice don't show a significant change in total serum immunoglobulins or plasma cell numbers in the spleen or bone marrow.
How should I proceed? My first thought is to do a BLAST search for a homologous gene to factor X in the mouse genome. Maybe a factor Y has the same function as factor X. Deleting only Y should have the same as the deletion of X. A second experiment which deletes X and Y should then have the desired effect.
Is there anything else that would make sense?
Also, I think 6 months is quite young for mice, yes? So maybe factor X becomes only relevant later in life? If that is true, then observing the mice longer should so a decrease in plasma cells.
I hope the question is clear. Please let me know, if I should change it.