GATA4 is essential for jejunal function in mice. Gastroenterology 2008 Nov;135(5):1676-1686.e1
Date
09/25/2008Pubmed ID
18812176Pubmed Central ID
PMC2844802DOI
10.1053/j.gastro.2008.07.074Scopus ID
2-s2.0-55249123809 (requires institutional sign-in at Scopus site) 78 CitationsAbstract
BACKGROUND & AIMS: Although the zinc-finger transcription factor GATA4 has been implicated in regulating jejunal gene expression, the contribution of GATA4 in controlling jejunal physiology has not been addressed.
METHODS: We generated mice in which the Gata4 gene was specifically deleted in the small intestinal epithelium. Measurements of plasma cholesterol and phospholipids, intestinal absorption of dietary fat and cholesterol, and gene expression were performed on these animals.
RESULTS: Mice lacking GATA4 in the intestine displayed a dramatic block in their ability to absorb cholesterol and dietary fat. Comparison of the global gene expression profiles of control jejunum, control ileum, and GATA4 null jejunum by gene array analysis revealed that GATA4 null jejunum lost expression of 53% of the jejunal-specific gene set and gained expression of 47% of the set of genes unique to the ileum. These alterations in gene expression included a decrease in messenger RNAs (mRNAs) encoding lipid and cholesterol transporters as well as an increase in mRNAs encoding proteins involved in bile acid absorption.
CONCLUSIONS: Our data demonstrate that GATA4 is essential for jejunal function including fat and cholesterol absorption and confirm that GATA4 plays a pivotal role in determining jejunal vs ileal identity.
Author List
Battle MA, Bondow BJ, Iverson MA, Adams SJ, Jandacek RJ, Tso P, Duncan SAMESH terms used to index this publication - Major topics in bold
AnimalsCholesterol, Dietary
DNA
Dietary Fats
Enterocytes
GATA4 Transcription Factor
Gene Expression
Ileum
Immunohistochemistry
Intestinal Absorption
Jejunum
Mice
Reverse Transcriptase Polymerase Chain Reaction
Zinc Fingers
