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Originally published In Press as doi:10.1074/jbc.M201601200 on December 18, 2002

J. Biol. Chem., Vol. 278, Issue 9, 7600-7606, February 28, 2003
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Developmental Regulation of Apolipoprotein B mRNA Editing Is an Autonomous Function of Small Intestine Involving Homeobox Gene Cdx1*

Amy P. PattersonDagger §, Zhigang ChenDagger , Deborah C. Rubin, Virginie Moucadel||, Juan Lucio Iovanna||, H. Bryan Brewer Jr.**, and Thomas L. EggermanDagger Dagger §§

From the Dagger  NHLBI, National Institutes of Health, Bethesda, Maryland 20892,  Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, || Laboratoire de Recherche de Physiologie et Pathologie Digestives, INSERM E.116, 13009 Marseille, France, ** Molecular Disease Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, Dagger Dagger  Division of Diabetes, Endocrinology and Metabolic Diseases, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, and §§ Department of Laboratory Medicine, W. G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892

Apolipoprotein B mRNA editing is developmentally regulated in the human and rodent small intestine, changing from <1% at day 14 to ~90% by day 20 in the rat fetus. This regulation is coincident with the developmental formation of the crypt-to-villus axis functional unit, a continuous and rapidly renewing system involving cell generation, migration, and differentiation. Utilizing small intestine isografts implanted into the subcutaneous tissue of adult recipients, apolipoprotein B mRNA editing was developmentally up-regulated, parallel to that seen with an intact control. In contrast, apoB mRNA expression remains nearly constant in the isograft, unlike the normal intact small intestine. Immunohistochemical analyses demonstrated that apoB-48 protein existed predominantly in well differentiated enterocytes along the villus surface whereas apoB-100 was in the lamina propria and crypts. ApoB mRNA editing levels were very low in the crypt-like rat intestinal cell line, IEC-6 (~0.3%), but very high in well differentiated enterocytes (~91.5%). The expression of homeobox gene Cdx1 increased 18-fold in small intestine in vivo during the same time course when apoB mRNA editing increased from ~2 to ~90%. The overexpression of Cdx1 in IEC-6 cells increased apoB mRNA editing over 10-fold compared with the vector control. This increase was associated with a significant increase of activating factor ACF, a component of the apoB mRNA editing complex. Taken together, these data suggest that the developmental regulation of apoB mRNA editing is an autonomous cytodifferentiation function of small intestine for which homeobox gene Cdx1 may play an important role.

* This work was supported in part by National Institutes of Health Grant R01-DK46122 (to D. C. R.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ To whom correspondence should be addressed: Office of Biotechnology Activities, NIH, 6705 Rockledge Dr., Suite 750, Bethesda, MD 20892. Tel.: 301-496-9838; Fax: 301-496-9839; E-mail: pattersa@od.nih.gov.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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