Tracking LINE1 retrotransposition in the germline

Nearly half of the mammalian genome is occupied by repetitive transposon elements, including long-interspersed nuclear elements (LINEs), short-interspersed nuclear elements, and long terminal repeat retrotransposons. The ability of these transposable elements to propagate and insert randomly throughout the genome plays an important role in genome evolution (1). However, as transposon-mediated insertional mutagenesis has been shown to play a causative role in >65 human genetic diseases (2), it is critical that this process be tightly controlled, particularly in the germline. Remarkably, LINEs account for about one-fifth of the human or mouse genome (3), the majority of which are LINE1 (∼600,000 copies in the murine genome). LINE1 is an active and autonomous transposable element that propagates in the genome through retrotransposition, whereby a LINE1 transcript is reverse-transcribed and inserted into the genome at a different location. The full-length LINE1 encodes two proteins: ORF1p and ORF2p, both of which are needed for its mobilization. Because of its repetitive and highly abundant nature, it is nearly impossible to track the activity of individual endogenous LINE1 elements in animals. As reported in PNAS, Newkirk et al. have overcome this hurdle by generating a new LINE1 reporter transgene in mouse (4). Although a number of LINE1 transgenic mouse models have been reported, these transgenes used either human LINE1 elements or non-LINE1 promoters (5⇓⇓–8), and therefore may not fully recapitulate the expression and activity of endogenous mouse LINE1 elements. Newkirk et al. (4) generated new LINE1 transgenes in which expression was driven under the control of the endogenous mouse LINE1 promoter encoded within its own 5′UTR. This new transgene consists of codon-optimized mouse ORF1 and ORF2 for improved translation …