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. 1991 Nov 1;88(21):9407–9411. doi: 10.1073/pnas.88.21.9407

Use of transgenic mice to infer the biological properties of small intestinal stem cells and to examine the lineage relationships of their descendants.

K A Roth 1, M L Hermiston 1, J I Gordon 1
PMCID: PMC52726  PMID: 1946352

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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