Zinc-inducible expression systems

Zinc-inducible expression systems (P j ZitR-driven Heterologous Expression and Zirex) ... 

More recently, a new zinc-inducible expression system, called Zirex, was developed for L. Metis (Mu et al. 2013). When triggered by a non-toxic concentration of zinc, the streptococcal promoter PczcD (regulated by the SezA repressor) is activated and leads to elevated expression levels. Moreover, Mu and colleagues have successfully combined both the NICE system and Zirex to produce different proteins at different times in the same microorganism. 

Since this promoter can be induced by the addition of zinc, it allows for the conditional expression of genes. This induction is especially important if the expression of a particular gene is deleterious to the cell. For example, the adenomatous polyposis coli (APC) tumor suppressor gene was inserted into a vector downstream of the MT II promoter (Morin et al., 1996). Since continuous expression of APC is inhibitory to cell growth, an inducible expression system was necessary to examine the effects of APC expression on cells. This promoter was specifically chosen due to its low basal activity in the absence of zinc The drawbacks to this system are the potential effects that increased zinc concentrations may have in the cell. These effects may include toxicity to the cell or altered gene expression due simply to the presence of zinc. 

The lack of zinc can also be a problem in biological systems and is responsible for disease states. For example, nitric oxide-dependent apoptosis can be induced in motor neurons by zinc-deficient SOD, and in some cases of amyotrophic lateral sclerosis, zinc-deficient SOD may participate in this type of oxidative mechanism involving nitric oxide.969 One form of hereditary human hair loss or alopecia was mapped to a specific gene and a mutation found in affected individuals. The gene encodes a single zinc finger transcription factor protein with restricted expression in the brain and skin.970 Zinc has been implicated in Alzheimer s via beta amyloid formation, and a role has been attributed for the cerebral zinc metabolism in the neuropathogenesis of Alzheimer s disease.971... 

Experimental work has revealed a complex relationship between the vomeronasal and olfactory systems. Although the vomeronasal system mediates most of the classical primer effects, olfaction appears to regulate, in part, the expression of at least one. Normally, the reproductive systems of rats do not respond to shortened daylengths however, removal of the olfactory and accessory olfactory bulbs or intranasal zinc sulfate treatment, but not removal of the vomeronasal organ, induces photoperiodism in rats (Nelson et al., 1985). Furthermore, many behavioral responses to chemical cues are affected by lesion of the vomeronasal system (see Table 1). Hence, the vomeronasal system and olfaction modulate both primer and signaller effects, and may interact depending upon past experience. This latter contention has been pursued in our laboratories in studies of animals lacking the sensory afferents of the vomeronasal system. 

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