It is somewhat surprising that deletion of each of these genes caused either a decrease or no change (depending on the test) in drinking and none of the deletions increased drinking. This is particularly true for deletion of Il1rn which should cause an increase in IL-1 signaling, whereas the other deletions might be expected to decrease cytokine activity. However, given the complexity of this signaling system, this is likely an incorrect over-simplification. It is important not to assume that levels of mRNA and protein are always positively correlated and that the direction of mRNA changes reflects the direction of functional changes. Although in many cases changes in levels of mRNA predict changes in protein, no correlation or even a negative correlation has been observed because transcription, translation and mRNA and protein degradation are intrinsically dynamic processes regulated by independent mechanisms and time constraints (Lewandowski and Small; 2005; Jayapal et al., 2008). For example, activation of microglia or macrophages increases the secretion of cathepsin S, but decreases the level of the transcript (Liuzzo et al., 1999). The important point is the
