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A mouse model of human L1 retrotransposition

Nature Genetics volume 32, pages 655–660 (2002)Cite this article

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 mutagenesis1,2. 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.

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Figure 1: Transgenic mouse lines.
Figure 2: L1 transgene expression in germ cell fractions.
Figure 3: Expression from retrotransposition events in condensing-spermatid fractions.
Figure 4: PCR of germ-cell DNA to detect retrotransposition.
Figure 5: L1 insertions in transgenic mice.

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Acknowledgements

We thank A. Farley, K.-S. Kim and M.C. Cha for technical assistance; the Transgenic and DNA Sequencing Cores of the University of Pennsylvania for generation of transgenic mouse lines and for DNA sequences, respectively; and J. Moran and B. Brouha for critical reading of the manuscript. E.M.O. was supported by a Howard Hughes Predoctoral Fellowship, and H.H.K. was supported by grants from the US National Institutes of Health.

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Authors and Affiliations

  1. Department of Genetics and University of Pennsylvania School of Medicine, 475 Clinical Research Bldg., 415 Curie Blvd., Philadelphia, 19104, Pennsylvania, USA

    Eric M. Ostertag, Ralph J. DeBerardinis, John L. Goodier, Yue Zhang, Nuo Yang & Haig H. Kazazian Jr.

  2. Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, 475 Clinical Research Bldg., 415 Curie Blvd., Philadelphia, 19104, Pennsylvania, USA

    George L. Gerton

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  1. Eric M. Ostertag
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  2. Ralph J. DeBerardinis
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Correspondence to Haig H. Kazazian Jr..

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Ostertag, E., DeBerardinis, R., Goodier, J. et al. A mouse model of human L1 retrotransposition. Nat Genet 32, 655–660 (2002). https://doi.org/10.1038/ng1022

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