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Cell type-specific and efficient synthesis of human cytokeratin 19 in transgenic mice.

In studies designed to identify cis-regulatory elements involved in the cell-type-specific expression of human cytokeratin (CK) genes we have dissected from the major type I CK gene locus on chromosome 17 a region containing the gene that encodes CK 19, with flanking segments of different lengths, and have examined the expression of related gene constructs in transgenic mice. Adult transgenic mice have been characterized by immunohistochemistry, gel-electrophoretic analyses of cytoskeletal proteins and genomic DNA (Southern blots). We have found that a construct harbouring the transcriptional unit plus approximately 0.7 kb downstream from the polyA-addition site and an immediately adjacent 5' upstream segment of approximately 3.6 kb, when combined with a further 5' upstream element of -6.4 - -8.6 kb, is sufficient to guarantee the synthesis of human CK 19 in the same cells and to a similar extent as the murine genome expresses its endogenous CK 19 gene. The findings demonstrate that all cis-elements necessary for the specific and efficient expression of a single type I CK gene, in the context of epithelial differentiation, can be located in the vicinity of the gene itself and that more-distant elements are not required.