HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M500556-JLR200v1 47/4/734    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Beigneux, A. P. Articles by Young, S. G. Search for Related Content PubMed PubMed Citation Articles by Beigneux, A. P. Articles by Young, S. G. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 47, 734-744, April 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Agpat6—a novel lipid biosynthetic gene required for triacylglycerol production in mammary epithelium

Anne P. Beigneux^1,*, Laurent Vergnes, Xin Qiao^*, Steven Quatela, Ryan Davis^**, Steven M. Watkins^**, Rosalind A. Coleman, Rosemary L. Walzem^**, Mark Philips, Karen Reue and Stephen G. Young^*

^* Division of Cardiology, Department of Internal Medicine, University of California, Los Angeles, CA 90095
Departments of Medicine and Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073
Department of Medicine, Cell Biology, and Pharmacology, New York University School of Medicine, New York, NY 10016
^** Lipomics Technologies, West Sacramento, CA 95691
Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599

Published, JLR Papers in Press, January 31, 2006.

¹ To whom correspondence should be addressed. e-mail: abeigneux{at}mednet.ucla.edu

In analyzing the sequence tags for mutant mouse embryonic stem (ES) cell lines in BayGenomics (a mouse gene-trapping resource), we identified a novel gene, 1-acylglycerol-3-phosphate O-acyltransferase (Agpat6), with sequence similarities to previously characterized glycerolipid acyltransferases. Agpat6's closest family member is another novel gene that we have provisionally designated Agpat8. Both Agpat6 and Agpat8 are conserved from plants, nematodes, and flies to mammals. AGPAT6, which is predicted to contain multiple membrane-spanning helices, is found exclusively within the endoplasmic reticulum (ER) in mammalian cells. To gain insights into the in vivo importance of Agpat6, we used the Agpat6 ES cell line from BayGenomics to create Agpat6-deficient (Agpat6^–/–) mice. Agpat6^–/– mice lacked full-length Agpat6 transcripts, as judged by northern blots. One of the most striking phenotypes of Agpat6^–/– mice was a defect in lactation. Pups nursed by Agpat6^–/– mothers die perinatally. Normally, Agpat6 is expressed at high levels in the mammary epithelium of breast tissue, but not in the surrounding adipose tissue. Histological studies revealed that the aveoli and ducts of Agpat6^–/– lactating mammary glands were underdeveloped, and there was a dramatic decrease in the size and number of lipid droplets within mammary epithelial cells and ducts. Also, the milk from Agpat6^–/– mice was markedly depleted in diacylglycerols and triacylglycerols. Thus, we identified a novel glycerolipid acyltransferase of the ER, AGPAT6, which is crucial for the production of milk fat by the mammary gland.

Supplementary key words acyltransferase • transacylase • milk fat

Abbreviations: AGPAT, 1-acylglycerol-3-phosphate O-acyltransferase; DGAT, diacylglycerol acyltransferase; ECFP, enhanced cyan fluorescent protein; ER, endoplasmic reticulum; ES, embryonic stem; GNPAT, glyceronephosphate O-acyltransferase; GPAM, glycerol-3-phosphate acyltransferase; LYCAT, lysocardiolipin acyltransferase

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. E. Gimeno and J. Cao Thematic Review Series: Glycerolipids. Mammalian glycerol-3-phosphate acyltransferases: new genes for an old activity J. Lipid Res., October 1, 2008; 49(10): 2079 - 2088. [Abstract] [Full Text] [PDF]

				J. Cao, D. Shan, T. Revett, D. Li, L. Wu, W. Liu, J. F. Tobin, and R. E. Gimeno Molecular Identification of a Novel Mammalian Brain Isoform of Acyl-CoA:Lysophospholipid Acyltransferase with Prominent Ethanolamine Lysophospholipid Acylating Activity, LPEAT2 J. Biol. Chem., July 4, 2008; 283(27): 19049 - 19057. [Abstract] [Full Text] [PDF]

				M. Bionaz and J. J. Loor ACSL1, AGPAT6, FABP3, LPIN1, and SLC27A6 Are the Most Abundant Isoforms in Bovine Mammary Tissue and Their Expression Is Affected by Stage of Lactation J. Nutr., June 1, 2008; 138(6): 1019 - 1024. [Abstract] [Full Text] [PDF]

				Y. Q. Chen, M.-S. Kuo, S. Li, H. H. Bui, D. A. Peake, P. E. Sanders, S. J. Thibodeaux, S. Chu, Y.-W. Qian, Y. Zhao, et al. AGPAT6 Is a Novel Microsomal Glycerol-3-phosphate Acyltransferase J. Biol. Chem., April 11, 2008; 283(15): 10048 - 10057. [Abstract] [Full Text] [PDF]

				C. A. Nagle, L. Vergnes, H. DeJong, S. Wang, T. M. Lewin, K. Reue, and R. A. Coleman Identification of a novel sn-glycerol-3-phosphate acyltransferase isoform, GPAT4, as the enzyme deficient in Agpat6-/- mice J. Lipid Res., April 1, 2008; 49(4): 823 - 831. [Abstract] [Full Text] [PDF]

				Y. Zhao, Y.-Q. Chen, T. M. Bonacci, D. S. Bredt, S. Li, W. R. Bensch, D. E. Moller, M. Kowala, R. J. Konrad, and G. Cao Identification and Characterization of a Major Liver Lysophosphatidylcholine Acyltransferase J. Biol. Chem., March 28, 2008; 283(13): 8258 - 8265. [Abstract] [Full Text] [PDF]

				E. Soupene, H. Fyrst, and F. A. Kuypers Mammalian acyl-CoA:lysophosphatidylcholine acyltransferase enzymes PNAS, January 8, 2008; 105(1): 88 - 93. [Abstract] [Full Text] [PDF]

				S. Jain, N. Stanford, N. Bhagwat, B. Seiler, M. Costanzo, C. Boone, and P. Oelkers Identification of a Novel Lysophospholipid Acyltransferase in Saccharomyces cerevisiae J. Biol. Chem., October 19, 2007; 282(42): 30562 - 30569. [Abstract] [Full Text] [PDF]

				A. K Agarwal, S. Sukumaran, R. Bartz, R. I Barnes, and A. Garg Functional characterization of human 1-acylglycerol-3-phosphate-O-acyltransferase isoform 9: cloning, tissue distribution, gene structure, and enzymatic activity J. Endocrinol., June 1, 2007; 193(3): 445 - 457. [Abstract] [Full Text] [PDF]

				J. Cao, J.-L. Li, D. Li, J. F. Tobin, and R. E. Gimeno Molecular identification of microsomal acyl-CoA:glycerol-3-phosphate acyltransferase, a key enzyme in de novo triacylglycerol synthesis PNAS, December 26, 2006; 103(52): 19695 - 19700. [Abstract] [Full Text] [PDF]

				K. Reue and L. Vergnes Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Approaches to lipid metabolism gene identification and characterization in the postgenomic era J. Lipid Res., September 1, 2006; 47(9): 1891 - 1907. [Abstract] [Full Text] [PDF]

				L. Vergnes, A. P. Beigneux, R. Davis, S. M. Watkins, S. G. Young, and K. Reue Agpat6 deficiency causes subdermal lipodystrophy and resistance to obesity J. Lipid Res., April 1, 2006; 47(4): 745 - 754. [Abstract] [Full Text] [PDF]