Location Effects on Expression of the Transgene

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).