Generation dependent reduction of tTA expression in double transgenic NZL-2/tTACMV mice

Lev Fedorov, Oleg Yu Tyrsin, Olena Sakk, Alla Ganscher, Ulf R. Rapp

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Despite the overall successful application of the tet-system to regulate gene expression in vitro and in vivo, nothing is known so far about the long-term stability of this system in transgenicmice. In this study, mice of generation F2, F3, F4, or F10 of two independent tTACMV transgenic lines were bred with NZL-2 mice containing a tTA-responsive bidirectional promoter that allows the simultaneous expression of two reporter genes encoding luciferase and β-galactosidase. Analysis of the expression of transgenes in double transgenic mice revealed a dramatic reduction of tTA transactivator mRNA over time. As a consequence, the expression of both reporter genes was gradually reduced from generation to generation in tissues of embryonic and adult NZL-2/t TACMV mice. Luciferase activity in NZL-2/ tTACMV(F10) mice was reduced 8-10-fold compared to NZL-2/ tTACMV(F2) mice, and β-galactosidase expression was no longer detectable. In summary, we describe the long-term instability of the tet-system in our NZL-2/tTACMV double transgenic mice. The molecular basis of this observation and experimental tools to overcome this limitation need to be addressed in future.

Original languageEnglish (US)
Pages (from-to)78-84
Number of pages7
JournalGenesis
Volume31
Issue number2
DOIs
Publication statusPublished - 2001
Externally publishedYes

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Keywords

  • mRNA
  • Tet system
  • Transcription
  • Transgenic mice
  • tTA

ASJC Scopus subject areas

  • Genetics

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