LOCATION
EFFECTS ON EXPRESSION OF THE TRANSGENE
Transgenic animals (or
plants) carrying the same inserted transgene often differ considerably in
expression. Both the level of expression and the pattern of expression in
various tissues of the body may vary. Many of these effects are due to the
location of the transgene. Expression of the inserted transgene will be
affected by any nearby regulatory elements already present in the host animal
chromosome. In particular, enhancer sequences work over considerable distances
and will affect the expression of any transgenes integrated nearby. In
addition, the physical state of the DNA is important. If the transgene is integrated
into a region that consists largely of heterochromatin, the transgene will be
expressed poorly or not at all. In such regions the DNA is tightly packed,
often methylated, covered with nonacetylated histones, and consequently usually
nontranscribed.
Such position effects have
been confirmed experimentally by extracting transgene DNA from a transgenic
animal in which the transgene was not expressed. This DNA was then used to
construct another line of transgenic animals. If some of the new transgenic
animals show proper expression of the transgene, this demonstrates that the
gene itself is intact and its failure to express in the original host animal
was due to its location (Fig. 15.6).
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