A 5'-upstream region of a bovine keratin 6 gene confers tissue-specific expression and hyperproliferation-related induction in transgenic mice.
Keratins, the constituents of epithelial intermediate filaments, are precisely regulated in a tissue- and development-specific manner, although little is known about the molecular mechanisms underlying this regulation. The expression pattern of keratin 6 is particularly complex, since besides being constitutively expressed in hair follicles and in suprabasal cells of a variety of internal stratified epithelia, it is induced in epidermis in both natural and artificially caused hyperproliferative situations. Therefore, the regulatory sequences controlling keratin 6 gene activity are particularly suitable for target gene expression in a tissue-specific manner. More interestingly, they can be skin-induced in transgenic animals or in gene therapy protocols, particularly those addressing epidermal hyperproliferative disorders. To delimit the regions containing these regulatory elements, different parts of the bovine keratin 6 gene linked to a beta-galactosidase reporter gene have been assayed in transgenic mice. A 9-kbp fragment from the 5' upstream region was able to provide both suprabasal tissue-specific and inducible reporter expression.
Ramírez
A
A
Department of Cell and Molecular Biology, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid, Spain.
Vidal
M
M
Bravo
A
A
Larcher
F
F
Jorcano
J L
JL
D000818:Animals; D002417:Cattle / Q000235:genetics*; D002455:Cell Division; D002874:Chromosome Mapping; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006197:Hair / Q000166:cytology / Q000378:metabolism; D007633:Keratins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D012867:Skin / Q000166:cytology / Q000378:metabolism; D001616:beta-Galactosidase / Q000096:biosynthesis
D007633:Keratins; D001616:beta-Galactosidase