Limited transcription of rat elastase I transgene repeats in transgenic mice

The rat elastase I (EI) regulatory region is an enhancer that directs efficient pancreas-specific transcription of linked genes integrated in the chromosomes of transgenic mice. However, with increasing numbers of tandemly repeated EI transgenes, the transcription rate per gene decreased. This decrease was not due to a titration of essential transcription factors, because transgenic mice with as many as 250 copies of the rat EI enhancer continued transcription of the endogenous mouse EI gene at its normal rate. Furthermore, when transgenic mice bearing 250 EI genes and mice bearing 7 copies of an EI enhancer-directed human growth hormone (hGh) gene were mated to produce mice with two unlinked arrays of EI enhancer-driven transgenes, each array was transcribed at the same rate as in mice bearing each array separately. Long tandem arrays of transgenes may inhibit efficient transcription despite the presence of ample amounts of essential transcription factors. Although the transcription rate of the mouse EI gene was not affected by the presence of large numbers of transgenes, the amounts of mouse elastase I and elastase II mRNAs were decreased in the presence of high levels of transgene mRNA, indicating an adjustment of the cell mRNA population.