The Temporal Control of Gene Expression

Specialized proteins bind to the control regions of a gene (called promoters or operators) and increase or decrease the probability of transcription. In bacteria, genes to counter tetracycline antibiotics are kept switched off by the binding of a repressor protein to the appropriate operon (bacterial control sequence). Tetracyclines bind to the repressor and release it from the operon, permitting gene expression. A useful mutation of this system works in reverse: An activator of transcription does not bind the control region unless tetracycline is present so that antibiotic switches the system on. Insertion of these bacterial genes into mammals can be used to provide precise temporal control of gene expression. In one mouse, the activator protein (called rtTA) is placed under the control of calcium/calmodulin kinase, so it is expressed abundantly, but only in the forebrain. A second mouse has a transgene inserted that is under the control of tetO, the region of DNA to which rtTA binds. Progeny of these two mice will show elevated gene expression in the forebrain in response to a tetracycline-class antibiotic, such as doxycyclin. A proof-of-concept study used calcineurin as the transgene. Calcineurin is a protein phosphatase, and as a simplistic model it predicts that if protein phosphorylation by specific kinases is critical for the induction of LTP and for memory, then overexpression of phosphatases such as calcineurin should neutralize the kinase effects by dephosphor-ylating some of the critical proteins. This is indeed the case: The mutant progeny show normal LTP and a normal ability to recall their spatial training until doxycyclin is added to their food. Doxycyclin treatment significantly decreases both LTP and the ability to retrieve (recall) spatial training. When doxycyclin is withdrawn and the antibiotic clears from the animals' bodies, their LTP and ability to recall training revert to normal. Doxycyclin treatment does not alter the characteristics of the parental strains, which contain the individual components of the expression control system.

Breaking Bulimia

Breaking Bulimia

We have all been there: turning to the refrigerator if feeling lonely or bored or indulging in seconds or thirds if strained. But if you suffer from bulimia, the from time to time urge to overeat is more like an obsession.

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