GATA4 is essential for jejunal function in mice.
OBJECTIVE
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.
Battle
Michele A
MA
Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Bondow
Benjamin J
BJ
Iverson
Moriah A
MA
Adams
Scott J
SJ
Jandacek
Ronald J
RJ
Tso
Patrick
P
Duncan
Stephen A
SA
D000818:Animals; D002791:Cholesterol, Dietary / Q000493:pharmacokinetics; D004247:DNA / Q000235:genetics*; D004041:Dietary Fats / Q000493:pharmacokinetics; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism; D050991:GATA4 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression; D007082:Ileum / Q000166:cytology / Q000502:physiology; D007150:Immunohistochemistry; D007408:Intestinal Absorption / Q000502:physiology*; D007583:Jejunum / Q000166:cytology / Q000502:physiology*; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016335:Zinc Fingers
D002791:Cholesterol, Dietary; D004041:Dietary Fats; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D004247:DNA