Conditional activation of a single-copy L1 transgene in mice by Cre

Wenfeng An, Jeffrey S. Han, Christina M. Schrum, Anirban Maitra, Frank Koentgen, Jef D. Boeke

Research output: Contribution to journalArticlepeer-review

Abstract

The synthetic L1 retrotransposon, ORFeus, is useful for probing mechanisms of L1 retrotransposition in vivo and for genome-wide mouse mutagenesis because of its high level of activity. To achieve controlled activation of ORFeus in mice, we constructed ORFeusLSL, in which ORFeus coding sequences were separated from the promoter by a loxP-β-geo-stop-loxP (LSL) cassette, and derived transgenic mouse lines containing single-copy ORFeusLSL. We observed tissue-specific ORFeus activation by crosping ORFeusLSL to various Cre-expressing lines, specifically in the germ line or the pancreas, providing definite evidence that all host factors and machinery required posttranscriptionally for L1 retrotransposition are available in somatic tissues in living animals. Notably, the single-copy ORFeus transgene is about threefold more active per copy than a previously described multicopy ORFeus transgene in the germ line and even more active somatically. This conditional transgenic ORFeus mouse model should allow further exploration of posttranscriptional cellular requirements for L1 retrotransposition and facilitate the development of ORFeus mouse lines suitable for in vivo mutagenesis.

Original languageEnglish (US)
Pages (from-to)373-383
Number of pages11
JournalGenesis
Volume46
Issue number7
DOIs
StatePublished - Jul 2008

Keywords

  • Conditional
  • Copy number
  • Cre/Iox system
  • LINE-1
  • Retrotransposon
  • Transgenic mouse

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Cell Biology

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