Use of transgenic mice to map cis-acting elements in the liver fatty acid-binding protein gene (Fabpl) that regulate its cell lineage-specific, differentiation-dependent, and spatial patterns of expression in the gut epithelium and in the liver acinus.

作者：Theodore C. Simon, Kevin A. Roth, Jeffrey I. Gordon · 发表于：Journal of Biological Chemistry · 年份：1993 · DOI：10.1016/s0021-9258(17)46851-7 · 被引用次数：125 · 研究领域：Peroxisome Proliferator-Activated Receptors、Drug Transport and Resistance Mechanisms、Metabolism and Genetic Disorders

Axial pattern formation is sustained in the mammalian gut epithelium despite rapid and continuous renewal of its four principal cell lineages. The mouse and rat liver fatty acid-binding protein (L-FABP) genes (Fabpl) represent an excellent model for understanding the mechanisms that determine differentiation-dependent, cell lineage-specific, and distinct regional patterns of expression along the crypt-to-villus and duodenal-to-ileal axes of the gut, as well as within the liver acinus. We have used transgenic mice to map cis-acting elements in rat Fabpl that control these patterns of gene expression. Seven transgenes were analyzed, representing sequential deletions of the 5'-nontranscribed domain of Fabpl linked to the human growth hormone (hGH) gene beginning at its nucleotide +3 (L-FABP/hGH+3). Several pedigrees of mice containing each one of the L-FABP/hGH+3 transgenes were examined at the end of their 8th and 20th weeks of postnatal life using immunocytochemical and RNA hybridization analyses. A remarkably compact sequence spanning nucleotides -132 to +21 of Fabpl is sufficient to establish and maintain a distribution of reporter mRNA and protein in villus-associated enterocytes located along the duodenal-to-ileal axis of the gut that resembles the pattern of expression of the endogenous Fabpl gene. L-FABP-132 to +21/hGH+3 is also expressed in surface and pit mucous cells of gastric units and in enterocytes located in the colonic homologs of small intestinal villi, the sur...