Copy-Dependent and Position-Independent Expression of Rat Aldolase A Gene1

Abstract

In order to understand the molecular mechanisms of the temporal and spatial differences of gene expression in higher organisms, rat aldolase A gene carrying two distinct promoters was introduced into fertilized eggs and the resulting transgenic mice were analyzed. The transgene expression is tissue-specific and is developmentally regulated. In addition, the expression is regulated in a copy-dependent manner irrespective of where the transgene is integrated, suggesting that a mechanism excluding the effect of the integration site exists within the transgene itself. To explore the conformational change of this gene in the genome, the DNase I hypersensitive sites of the gene were examined. Three sites (DHS-1,2, and 3) were identified upstream and downstream of the gene and these sites were retained in the transgene as well as in the gene observed endogenously.

Efficient Male and Female Germline Transmission of a Human Chromosomal Vector in Mice

“…This introduction of foreign DNA mutates the host genome: The transgene can modify the properties of neighboring host genes, whereas the host genome itself can influence transgene expression (Robertson et al 1995;Rivella and Sadelain 1998). In addition, often more than one copy of the transgene is introduced in the host genome (Hashido et al 1995;Garrick et al 1998) and the insertion of foreign DNA can lead to rearrangements and deletions (Choi et al 1993;Strauss et al 1993). Episomal vectors such as those containing the latent origin of replication oriP from the herpes Epstein-Barr-virus replicate once every cell cycle in cells expressing its transactivator EBNA-1 and allow the introduction and long-term expression of foreign DNA in human cell lines.…”