Based knockdown

Achenbach T V, Brnnner B, Heermeier K (2003). Oligonncleotide-based knockdown technologies Antisense versns RNA interference. Chembiochem. 4 928-935. 

Unlike the Gre/loxP system, the tetR/O switch is not dependent on enzyme-based DNA rearrangements but is controlled by the small synthetic compound doxycycline (Dox). In the absence of Dox the tetracycline repressor (tetR), expressed from a constitutive promoter, binds to the tet operator (tetO) within a modified HI promoter and blocks shRNA transcription (Fig. 3b). Exposure to Dox dissociates the tetR from tetO which enables shRNA expression from the HI promoter (22). Thus, gene silencing is induced by Dox addition (20, 22, 23). This system is successfully in use to validate the potential of candidate drug targets in vivo (24-28). A commercial service for the production of Dox inducible knockdown mice and rats is available from Taconic (see www. taconic.com). 

Kotnik K, Popova E, Todiras M et al (2009) Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown. PLoS One 4 e5124... 

Viral vectors allow the generation of a stable knockdown, as their shRNA-containing genomes integrate into the host cell and thus replicate with each cell division. This is an important distinguishing characteristic of a viral-based approach, and is necessary for experiments that require more than the 2- to 10-day window of knockdown. Researchers must pay particular attention to validating... 

To determine whether inhibitors specifically inhibit the PTP of interest in primary human T cells, purified T cells can be used, in which the target PTP has been acutely eliminated (residual expression <20 % of normal expression) by short interfering RNA (siRNA)- or small hairpin RNA (shRNA)-mediated knockdown. Signaling in T cells with severely reduced protein levels of the PTP of interest is expected to be similar to signaling in T cells treated with a specific inhibitor of the PTP. However, this may not always be the case. Inhibition of PTP activity by the inhibitor, or eliminating the protein altogether via RNAi, may have different outcomes due to a more complex function of the PTP that is not based on its phosphatase activity alone [31]. Nonetheless, the combined action of PTP inhibitor and PTP knockdown should not alter signaling beyond what is observed for each alone. 

The products are based on inert materials such as silica gel or diatomaceous earth (DE) and contain no insecticides or knockdown agents. They are effective against species resistant to pesticides, and are stable at high and low temperatures (McLaughlin, 1994). In contrast to chemical insecticides, which induce rapid immobilisation and kill, the action of inert dusts is slow, and extended exposure periods of 20 days or more may be required to eliminate an insect population. Most products, at the appropriate concentration, provide protection for at least 12 months (McLaughlin, 1994). 

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