The lactase-phlorizin hydrolase (LPH) gene, which is expressed in a well characterized cell- and developmental- specific pattern will be used as a marker to study the mechanisms of gene regulation in the intestine. Not only is LPH specific to the enterocyte; in rat, rabbit, and human, lPH expression occurs concomitantly with the process of intestinal morphogenesis in the fetus. The proposed studies seek to determine the factors that control the pattern of lPH expression and ultimately to examine the importance of these factors in intestinal development and differentiation. Preliminary work has centered on cloning the 5'-flanking region of the rat LPH gene and establishing a cell cultur model for transient transfection studies using LPH flanking region-reporter fusion genes. Preliminary data suggest the presence of both positive and negative control elements within 2 kilobases of the transcription unit. The proposed studies intend to: identify and q precisely map cis-acting elements in the 5'-flanking sequence of the rat LPH gene responsible for developmental and cell-specific expression; identify and characterize specific nuclear proteins that interact with these elements; and identify the elements in the rat LPH gene necessary to direct correct expression of LPH in transgenic mice.
| Verhave, Menno; Krasinski, Stephen D; Christian, Sara I et al. (2004) Regulatory regions in the rat lactase-phlorizin hydrolase gene that control cell-specific expression. J Pediatr Gastroenterol Nutr 39:275-85 |
| Krasinski, S D; Upchurch, B H; Irons, S J et al. (1997) Rat lactase-phlorizin hydrolase/human growth hormone transgene is expressed on small intestinal villi in transgenic mice. Gastroenterology 113:844-55 |
