Variegation and silencing in a lentiviral-based murine transgenic model |
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Authors: | Delphine Baup Laurent Fraga Eileen Pernot Annette Van Acker Anne-Sophie Vanherck Karine Breckpot Kris Thielemans Stéphane Schurmans Muriel Moser Oberdan Leo |
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Affiliation: | 1.Laboratoire de Physiologie Animale, Faculté des Sciences,Institut de Biologie et de Médecine Moléculaire, Université Libre de Bruxelles,Gosselies,Belgium;2.Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Faculté de Médecine,Université Libre de Bruxelles,Gosselies,Belgium;3.Laboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology,Medical School of the Vrije Universiteit Brussel,Brussel,Belgium |
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Abstract: | 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. |
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