The keratin 19 promoter is potent for cell-specific targeting of genes in transgenic mice

(Background & Aims) under bar: Keratins are intermediate filaments that are critical in cytoskeletal organization. Their roles in cellular processes a re underscored by inherited human diseases in which germline mutations of k eratins are found, as well as by transgenic and knockout mouse models that recapitulate those diseases. Keratin 19 (K19) has unique structural propert ies and developmental and spatial expression patterns. This suggests that K 19 expression may correlate with important cell fate decisions in gastroint estinal tract epithelia, (Methods) under bar: We used mouse K19 5' untransl ated region and promoter sequences and fused it to the lacZ reporter gene i n a transgene construct. Characterization was by beta -galactosidase expres sion and X-gal histochemistry in gastrointestinal epithelia, Because endoge nous K19 protein is transcriptionally regulated by the Kruppel-like transcr iption factor 4 (KLF4), we determined the spatial expression patterns of KL F4 and K19 in relationship to the lacZ reporter gene product. (Results) und er bar: K19-lacZ transgenic mice were found to have reporter gene expressio n in an epithelial-specific pattern. Expression was restricted to ductal ep ithelial cells in the pancreas, surface colonocytes, small intestinal villi , and gastric isthmus cells. Transgene expression correlated with K19 and K LF4 protein expression in the pancreas and stomach and was overlapping in t he small and large intestine, (Conclusions) under bar: The K19 promoter may be a useful tool to study epithelial cell biology and subsequent transdiff erentiation programs, particularly the pancreas and stomach.