Transposable elements (TE) are mobile genes able to move around the genome generating new endogenous mutations. Retrotransposons are a subset of TE’s that move via a copy and paste mechanism called retrotransposition whereby the total number of these elements increases. The only autonomously mobile TE in mammals is the retrotransposon Long interspersed nuclear elements (LINEs/L1).
Since retrotransposition results in new insertional mutations, it stands to reason this random process can result in cellular dysfunction when insertions occur within crucial genes or regulatory regions having over 100 cases of human genetic disease caused by L1 mediated retrotransposition. New insertions are also a driving force of evolution generating genetic diversity within a population, and even generating genetic mosaicism within an individual. At early developmental stages, retrotransposition events can generate somatic mosaicism in organisms by causing mutations that are inherited by every cell within that developmental lineage.
So, to study L1 retrotransposition in cell culture and transgenic animal models, fluorescent reporters have been used which mark cells containing new insertions with fluorescent proteins. This system has been demonstrated in cultured PA-1 embryonal carcinoma cells to undergo reporter silencing, leading to underestimations of L1 activity in vivo.
To combat epigenetic silencing the L1-Cre reporter construct was developed. In this system, Cre recombinase is used as the reporter, where as few as four molecules of Cre recombinase can activate a secondary reporter placed in a safe harbour locus, marking the cell with a fluorescent protein.
Ultimately the L1-Cre system will be used in combination with transgenic mice containing multicolour conditional reporter genes to circumvent potential L1 reporter silencing, while allowing for multispectral visualisation and analysis of genetic mosaicism driven by L1’s arising during mouse embryonic development.