Nucleic Acids Research, Vol 24, Issue 8 1465-1471, Copyright © 1996 by Oxford University Press
G Robertson, D Garrick, M Wilson, DI Martin and E Whitelaw
Variegation of transgene expression, a heterocellular or mosaic pattern of
expression seen in all mice in a given transgenic line, is a frequently
observed but unexplained phenomenon. We have encountered variegation with
globin transgenes; when lacZ expression is driven by globin control
elements a proportion of erythrocytes express beta- galactosidase
(beta-gal), while the remaining erythrocytes express none. The percentage
of expressing cells is constant within each line (at any particular
developmental stage), but varies between lines. Such variation may account
for much of the line-to-line variability which has been reported in the
expression of a transgene construct. We have now extended these
observations by studying expression of several globin/lacZ transgenes with
increasing age. Expression of beta-gal is variegated in all lines in adult
mice, including those made with a beta- globin promoter and locus control
region driving lacZ. The extent of variegation differs widely between
lines, but in all lines there is a marked decline in the number of
erythrocytes expressing beta-gal with increasing age. Progression of
silencing continues long past the point at which globin switching is
complete, suggesting that it is not related to this process. We observe
that age-dependent silencing is most severe in high copy number animals.
Increasing variegation of transgene expression with ageing of mice is
likely to complicate interpretation of the developmental regulation of
transgenes. We speculate that it reflects a general mechanism of epigenetic
regulation.
ARTICLES
Age-dependent silencing of globin transgenes in the mouse
Department of Biochemistry, University of Sydney, NSW, Australia.
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