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PMID: 2462524 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Mechanisms underlying generation of gradients in gene expression within the intestine: an analysis using transgenic mice containing fatty acid binding protein-human growth hormone fusion genes.

Genes & development ·Vol. 2 ·No. 10 ·1988-10-00 ·Pages 1318-32

Sweetser DA, Birkenmeier EH, Hoppe PC, McKeel DW, Gordon JI

Abstract

The intestine is lined by a continuously regenerating epithelium that maintains gradients in 'liver' fatty acid binding protein (L-FABP) gene expression along its horizontal and vertical axes, i.e., from duodenum to colon and from crypt to villus tip. To identify cis-acting DNA sequences responsible for these regional differences, we linked portions of the L-FABP gene's 5' nontranscribed region to the human growth hormone (hGH) gene and examined hGH expression in transgenic mice. Nucleotides -596 to +21 of the rat L-FABP gene correctly directed hGH expression to enterocytes and hepatocytes. However, anomalous expression was observed in small intestinal crypts, colon, and renal proximal tubular epithelial cells. Addition of nucleotides -4000 to -597 of the L-FABP gene, in either orientation, suppressed renal hGH expression and restored a nearly normal horizontal, but not a vertical, hGH gradient in the intestine. Thus, horizontal gradients of gene expression within the intestine can be maintained by orientation-independent, cis-acting suppressor elements.

MeSH Terms
Animals Base Sequence Carrier Proteins/biosynthesis,genetics Cloning, Molecular Epithelium/metabolism Fatty Acid-Binding Protein 7 Fatty Acid-Binding Proteins Growth Hormone/biosynthesis,blood,genetics Humans Immunoblotting Immunoenzyme Techniques Intestinal Mucosa/metabolism Kidney Tubules, Proximal/metabolism Liver/metabolism Mice Mice, Transgenic Mosaicism Neoplasm Proteins Nerve Tissue Proteins Nucleic Acid Hybridization Organ Specificity Promoter Regions, Genetic RNA/biosynthesis Radioimmunoassay Regulatory Sequences, Nucleic Acid Restriction Mapping Tumor Suppressor Proteins
Chemicals
Carrier Proteins FABP1 protein, human FABP7 protein, human Fabp1 protein, mouse Fabp1 protein, rat Fabp5 protein, mouse Fabp7 protein, mouse Fabp7 protein, rat Fatty Acid-Binding Protein 7 Fatty Acid-Binding Proteins Neoplasm Proteins Nerve Tissue Proteins Tumor Suppressor Proteins RNA Growth Hormone
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Sweetser D A
Department of Biological Chemistry, Washington University School of Medicine, St. Louis, Missouri 63110.
Birkenmeier E H
Hoppe P C
McKeel D W
Gordon J I
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
Published
1988-10-00
Pages
1318-32
Language
English
Region
United States
NLM ID
8711660
Subset
IM
Grants
NCI NIH HHS · 5P30-CA 34196-05 · United States
NIDDK NIH HHS · DK 30292 · United States
NIDDK NIH HHS · DK 34384 · United States
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