SITE-INDEPENDENT EXPRESSION OF THE CHICKEN BETA-A-GLOBIN GENE IN TRANSGENIC MICE

THE level of expression of exogenous genes carried by transgenic mice typically varies from mouse to mouse and can be quite low. This behaviour is attributed to the influence of the mouse chromatin near the site of transgene integration1,2. This 'position effect' has been seen in transgenic mice carrying the human β-globin gene. It was however, abolished when DNase I hypersensitive sites (normally found 65 to 44 kilobases (kb) upstream) were linked to the human β-globin transgene3-5. Thus, the upstream DNA (previously named a dominant control or locus activation region, now denoted a locus control region) conferred the ability to express human β-globin at high levels dependent on copy number on every mouse carrying the construct. We report here an investigation of chicken βA-globin gene expression in transgenic mice. A 4.5-kb fragment carrying the βA-globin gene and its downstream enhancer6-9, without any far upstream elements, is sufficient to ensure that every transgenic mouse expresses chicken globin messenger RNA at levels proportional to the transgene copy number. Thus the chicken DNA elements that allow position-independent expression can function in mice. In marked contrast to the human β cluster, these elements are no farther than 2 kb from the gene. The location of the elements within the cluster demonstrates that position independence can be mediated by DNA that does not define a gene cluster boundary. © 1990 Nature Publishing Group.