Effect of retinoid deficiency on keratin expression in mouse bladder

Twelve to sixteen weeks following treatment of CF-1 mice with a vitamin A-deficient diet, characteristic signs of retinoid deficiency including body wasting, poor hair coat, altered gait, decreased mobility, and xerophthalmia were observed. Histological examination of tissue sections from these mice revealed dramatic changes in the urinary tract epithelium. The normal transitional epithelium was replaced by a stratified squamous epithelium that resembled hyperproliferative epidermis. Using two-dimensional gel electrophoresis, a number of new proteins were found to be synthesized in vitamin A-deficient bladder when compared to tissue from control bladders. Using antikeratin antibodies in immunoblot experiments, we found that at least some of the newly synthesized proteins were keratins. These proteins, which comprise the intermediate filaments of the cytoskeleton, are known to be specific markers of epithelial differentiation. Of particular interest was the appearance of a Mr 67,000 basic and Mr 61,000 acidic keratin pair, characteristic of terminally differentiating murine epidermal cells. Unexpectedly, several other keratins, previously associated only with hyperproliferative epidermis, were also expressed in the tissue. These results demonstrate that vitamin A deficiency in the mouse leads to the appearance of a squamous metaplasia in the urinary tract epithelium that is characterized by the expression of distinct epidermal keratins.