Overexpressing FLP Recombinase Can Cause Synaptic Trafficking Defects in C. elegans
Site-specific recombinases, such as Cre recombinase (Cre) and FLP recombinase (FLPase), are popular tools that enable precise spatiotemporal control over fluorescent reporter genes. However, studies show that increased Cre expression can lead to cytotoxic phenotypes including DNA damage, cell cycle arrest, cell death, and aneuploidy. In contrast, there is little-to-no known cytotoxicity…
The use of FLP recombinase, a tool for precise spatiotemporal control over fluorescent reporter genes, can lead to unexpected consequences when expressed at high levels. According to researchers, increased expression of FLPase, the safer alternative to Cre recombinase, can disrupt synaptic protein trafficking in C. elegans. This discovery arose from the observation that high levels of FLPase from multi-copy extrachromosomal arrays caused mislocalization of a pre-synaptic marker, reduced abundance, transport, and expression of an ionotropic glutamate receptor subunit.
It was found that only single-copy expression of the FLPase construct did not trigger these off-target effects. The study highlights the importance of considering potential cytotoxicity at high doses of tyrosine recombinases like FLPase.
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