Genetics, Vol. 160, 1107-1112, March 2002, Copyright © 2002

Multiple Effects of Genetic Background on Variegated Transgene Expression in Mice

Margaret L. Opsahla, Margaret McClenaghana, Anthea Springbetta, Sarah Reida, Richard Latheb, Alan Colmanc, and C. Bruce A. Whitelawa
a Roslin Institute (Edinburgh), Division of Molecular Biology, Roslin, Midlothian, EH25 9PS, United Kingdom,
b Centre for Genome Research, University of Edinburgh, Edinburgh, EH9 3JQ, United Kingdom
c PPL Therapeutics, Roslin Biotechnology Centre, Roslin, Midlothian, EH25 9PP, United Kingdom

Corresponding author: C. Bruce A. Whitelaw, Division of Molecular Biology, Roslin, Midlothian, EH25 9PS, United Kingdom., bruce.whitelaw{at}bbsrc.ac.uk (E-mail)

Communicating editor: S. HENIKOFF

BLG/7 transgenic mice express an ovine ß-lactoglobulin transgene during lactation. Unusually, transgene expression levels in milk differ between siblings. This variable expression is due to variegated transgene expression in the mammary gland and is reminiscent of position-effect variegation. The BLG/7 line was created and maintained on a mixed CBA x C57BL/6 background. We have investigated the effect on transgene expression of backcrossing for 13 generations into these backgrounds. Variable transgene expression was observed in all populations examined, confirming that it is an inherent property of the transgene array at its site of integration. There were also strain-specific effects on transgene expression that appear to be independent of the inherent variegation. The transgene, compared to endogenous milk protein genes, is specifically susceptible to inbreeding depression. Outcrossing restored transgene expression levels to that of the parental population; thus suppression was not inherited. Finally, no generation-dependent decrease in mean expression levels was observed in the parental population. Thus, although the BLG/7 transgene is expressed in a variegated manner, there was no generation-associated accumulated silencing of transgene expression.




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