POSITION-DEPENDENT VARIEGATION OF A CD4 MINIGENE WITH TARGETED EXPRESSION TO MATURE CD4(-CELLS() T)

The CD4 gene follows a complex and highly regulated pattern of express ion throughout T cell development, This expression is governed by diff erent regulatory elements that have been partly identified, including a promoter, a proximal enhancer, and a silencer, Here we show that a C D4 minigene comprising a combination of these elements is specifically expressed in mature CD4(+) T cells of transgenic mice, but not in CD4 (+)CD8(+) double positive thymocytes, The proportion of transgene-expr essing CD4(+) T cells was constant within a given transgenic line, but varied greatly from one line to another. We demonstrate that this pat tern of expression is due to integration of the transgene within or in the vicinity of centromeric heterochromatin. This position-effect var iegation demonstrated with a short CD4 transgene has not been observed with larger ones containing additional regulatory sequences, suggesti ng that the CD4 gene contains a locus control region, Such position-de pendent effects must be taken into consideration when developing trans genic models or gene transfer vectors because they can result in the a bsence of transgene expression in a subpopulation of target cells, Fin ally, the combination of the CD4 gene silencer, proximal enhancer, and promoter provides an interesting tool to selectively express genes of interest in mature CD4(+) T cells of transgenic mice and for the deve lopment of gene therapy vectors.