title: A mouse model of human L1 retrotransposition.
abstract: The L1 retrotransposon has had an immense impact on the size and structure of the human genome through a variety of mechanisms, including insertional mutagenesis. To study retrotransposition in a living organism, we created a mouse model of human L1 retrotransposition. Here we show that L1 elements can retrotranspose in male germ cells, and that expression of a human L1 element under the control of its endogenous promoter is restricted to testis and ovary. In the mouse line with the highest level of L1 expression, we found two de novo L1 insertions in 135 offspring. Both insertions were structurally indistinguishable from natural endogenous insertions. This suggests that an individual L1 element can have substantial mutagenic potential. In addition to providing a valuable in vivo model of retrotransposition in mammals, these mice are an important step in the development of a new random mutagenesis system.
authors.affiliation: Department of Genetics and University of Pennsylvania School of Medicine, 475 Clinical Research Bldg., 415 Curie Blvd., Philadelphia, Pennsylvania 19104, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Ostertag
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: DeBerardinis
authors.forename: John L
authors.initials: JL
authors.lastname: Goodier
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Nuo
authors.initials: N
authors.lastname: Yang
authors.forename: George L
authors.initials: GL
authors.lastname: Gerton
authors.forename: Haig H
authors.initials: HH
authors.lastname: Kazazian
mesh_terms: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D000176:Acrosin / Q000378:metabolism; D000177:Acrosome / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D005819:Genetic Markers; D049452:Green Fluorescent Proteins; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D008957:Models, Genetic; D016254:Mutagenesis, Insertional; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D018626:Retroelements; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D005819:Genetic Markers; D008164:Luminescent Proteins; D012333:RNA, Messenger; D018626:Retroelements; D049452:Green Fluorescent Proteins; D004247:DNA; D000176:Acrosin