Variegation and silencing in a lentiviral-based murine transgenic model.
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.
Baup
Delphine
D
Laboratoire de Physiologie Animale, Faculté des Sciences, Institut de Biologie et de Médecine Moléculaire, Université Libre de Bruxelles, Gosselies, Belgium.
Fraga
Laurent
L
Pernot
Eileen
E
Van Acker
Annette
A
Vanherck
Anne-Sophie
AS
Breckpot
Karine
K
Thielemans
Kris
K
Schurmans
Stéphane
S
Moser
Muriel
M
Leo
Oberdan
O
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D018014:Gene Transfer Techniques; D016086:Lentivirus; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D034622:RNA Interference; D019076:Transgenes / Q000235:genetics
D017931:DNA Primers
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