title: Use of transgenic mice to infer the biological properties of small intestinal stem cells and to examine the lineage relationships of their descendants.
abstract: Transgenes, composed of elements of the 5' nontranscribed region of the liver fatty acid-binding protein (L-FABP) gene linked to various reporters, have previously been used to explore the cellular, regional, and temporal differentiation of the mouse intestinal epithelium. In this report, we have analyzed a pedigree of L-FABP/human growth hormone (hGH) transgenic mice that display a stable, heritable, mosaic pattern of reporter expression: wholly hGH-positive or hGH-negative populations of differentiating enterocytes arise from hGH-positive or hGH-negative crypts, respectively, and migrate as vertical coherent bands up the villus producing striped (polyclonal) villi. The ability of enteroendocrine cells within a given villus stripe to support hGH expression coincides with the enterocytic reporter phenotype, suggesting that these two terminally differentiated cells arise from a common multipotent stem cell. hGH-negative crypts are nonrandomly distributed around each villus and their frequency increases along the duodenal-to-ileal axis. Statistical analysis of the observed villus striping pattern suggests that transgene expression is not independently determined in individual crypts but rather in multicrypt "patches." The intact endogenous mouse L-FABP gene (Fabpl) exhibits a similar striped villus pattern of expression in a portion of the distal small intestine. These studies indicate that Fabpl and L-FABP/hGH transgenes represent sensitive markers for exploring the biological properties of gut stem cells and how positional information is encoded in this rapidly and continuously renewing epithelium.
authors.affiliation: Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: K A
authors.initials: KA
authors.lastname: Roth
authors.forename: M L
authors.initials: ML
authors.lastname: Hermiston
authors.forename: J I
authors.initials: JI
authors.lastname: Gordon
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D004847:Epithelial Cells; D004848:Epithelium / Q000502:physiology; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D013006:Growth Hormone / Q000235:genetics; D007082:Ileum / Q000166:cytology / Q000502:physiology; D007150:Immunohistochemistry; D007422:Intestines / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011401:Promoter Regions, Genetic; D011975:Receptors, Mitogen / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; C493319:FABP1 protein, human; C493320:Fabp1 protein, mouse; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011975:Receptors, Mitogen; D013006:Growth Hormone