title: L1 retrotransposition occurs mainly in embryogenesis and creates somatic mosaicism.
abstract: Long Interspersed Element 1 (L1) is a retrotransposon that comprises approximately 17% of the human genome. Despite its abundance in mammalian genomes, relatively little is understood about L1 retrotransposition in vivo. To study the timing and tissue specificity of retrotransposition, we created transgenic mouse and rat models containing human or mouse L1 elements controlled by their endogenous promoters. Here, we demonstrate abundant L1 RNA in both germ cells and embryos. However, the integration events usually occur in embryogenesis rather than in germ cells and are not heritable. We further demonstrate L1 RNA in preimplantation embryos lacking the L1 transgene and L1 somatic retrotransposition events in blastocysts and adults lacking the transgene. Together, these data indicate that L1 RNA transcribed in male or female germ cells can be carried over through fertilization and integrate during embryogenesis, an interesting example of heritability of RNA independent of its encoding DNA. Thus, L1 creates somatic mosaicism during mammalian development, suggesting a role for L1 in carcinogenesis and other disease.
authors.affiliation: Department of Genetics, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kano
authors.forename: Irene
authors.initials: I
authors.lastname: Godoy
authors.forename: Christine
authors.initials: C
authors.lastname: Courtney
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Vetter
authors.forename: George L
authors.initials: GL
authors.lastname: Gerton
authors.forename: Eric M
authors.initials: EM
authors.lastname: Ostertag
authors.forename: Haig H
authors.initials: HH
authors.lastname: Kazazian
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D016678:Genome / Q000235:genetics; D005838:Genotype; D005854:Germ Cells / Q000378:metabolism; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009030:Mosaicism; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic
chemical_list: D012313:RNA