Owing to the genetic complexity of higher eukaryotic cells and the absence of sophisticated genetic tools (compared to those for several microbial hosts), introduction of heterologous genetic information into mammalian hosts is usually achieved by cotransfection of a selection marker and the gene of interest with subsequent selection for clones containing the marker, and as empirical experience has shown, often also include the cotransfected gene (Kaufman and Sharp, 1982) . Many undesired phenomena accompany this haphazard genetic engineering of mammalian cells because of the undefined, mechanistically obscure selection of random integration sites in different stable clones, giving rise to variability in product expression levels, genetic stability, and second order effects on growth, viability, and productivity resulting from disruption of host genes (or regulatory loci) at the integration site. Recently, chromosomal locations of some industrially relevant mammalian cells lines have been found which show high transcription and stability for integration of transgenes (Karreman et al., 1996) . Screening for such sites is a time-consuming process that involves establishment of a genetic platform for subsequent targeted integration. However, unlike the situation in mouse ES stem cells (Hicks et al., 1997) gene targeting is difficult to achieve in most industrially relevant cell lines because they seem to lack necessary basic recombination machinery, and therefore they require installation of complex heterologous site-specific recombination systems (Fukushige and Sauer, 1992; Karreman et al., 1996) .