Specificity of Gene Expression and Insertional Mutagenesis in Transgenic Mice

Transgenic mice constitute an ideal system for determining the spatial and temporal control of gene expression in every conceivable tissue of the mammalian organism. A wide variety of gene constructs have been inserted in the mouse germ line, and the initial data compiled with this system have recently been reviewed by Gordon and Ruddle (1985) and by Palmiter and Brinster (1985). One of the most important conclusions from this initial work has been that expression of transferred genes may be directed to specific organs and tissues of the transgenic mouse, irrespective of the site of integration in the genome. In addition, a number of chimeric genes containing a 5′ flanking region of gene A and the coding sequence of gene B were found to express gene product B in the target tissue determined by gene A. Examples from our own laboratories that corroborate this fact include chimeric gene constructs composed of untranslated control regions of the mouse αA crystallin gene, mouse α2(I) collagen gene, or avian Rous sarcoma virus (RSV) and the bacterial sequence that encodes chloramphenicol acetyltransferase (CAT). In each instance, the upstream sequences exerted specific spatial and temporal controls on CAT expression in the transgenic mouse. A case in point is the αA crystallin control region that was found to produce the CAT enzyme selectively in the lens of the eye (Overbeek et al., 1985).