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Variegation and silencing in a lentiviral-based murine transgenic model.

journal article

Baup D, Fraga L, Pernot E, Van Acker A, Vanherck AS, Breckpot K, Thielemans K, Schurmans S, Moser M, Leo O.
Transgenic Res. 2009 Aug 23. [Epub ahead of print]

Lentiviral based constructs represent a recent development in the generation of transgenic animals. The ease of use, and the fact that the same backbone vectors can be used to down-modulate endogenous gene expression and to produce transgenic animals overexpressing a gene of interest, have fuelled growing interest in this technology. In this study, we have used a lentiviral delivery system to generate transgenic mice expressing altered levels (up or downregulated) of a gene of interest. Although this lentiviral-based approach led to high levels of transgenesis and germ line transmission, a wide variation in transgene expression was observed in most first and second generation mouse lines. In particular, despite the segregation of integrants into single-copy expressing mouse lines, transgene expression appeared to be the target of epigenetic regulatory mechanism, often causing the coexistence of high and low transgene expressing cells within a given tissue such as blood peripheral lymphocytes. The establishment and analysis of large number of mouse lines may therefore be required to select a stable transgenic line with pancellular expression of a gene of interest using this lentiviral-based approach.

URL: http://www.springerlink.com/content/tv323381x0h6n207/

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/19701794

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