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.

摘要: Axial pattern formation is sustained in the mammalian gut epithelium despite rapid and continuous renewal of its four principal cell lineages. The mouse rat liver fatty acid-binding protein (L-FABP) genes (Fabpl) represent an excellent model for understanding mechanisms that determine differentiation-dependent, lineage-specific, distinct regional patterns expression along crypt-to-villus duodenal-to-ileal axes gut, as well within acinus. We have used transgenic mice to map cis-acting elements Fabpl control these gene expression. Seven transgenes were analyzed, representing sequential deletions 5'-nontranscribed domain linked human growth hormone (hGH) beginning at nucleotide +3 (L-FABP/hGH+3). Several pedigrees containing each one L-FABP/hGH+3 examined end their 8th 20th weeks postnatal life using immunocytochemical RNA hybridization analyses. A remarkably compact sequence spanning nucleotides -132 +21 sufficient establish maintain a distribution reporter mRNA villus-associated enterocytes located axis resembles endogenous gene. L-FABP-132 +21/hGH+3 also expressed surface pit mucous cells gastric units colonic homologs small intestinal villi, epithelial cuffs. This transgene stomach colon recapitulates intact donor but not Fabpl, which silent proximal distal segments gastrointestinal tract. Analysis L-FABP-4000 +21/hGH+3, L-FABP-1600 L-FABP-596 L-FABP-246 L-FABP-186 indicate Fabpl's cephalocaudal gradient influenced by suppressors cecal between -4000 -1600 activators -597 -351. precociously activated proliferating nonproliferating crypts. suppressor(s) L-FABP accumulation crypt populations are represented +21, indicating different sequences regulate differentiation-dependent expression.(ABSTRACT TRUNCATED AT 400 WORDS)