文章基本信息

标题：Agpat6--a novel lipid biosynthetic gene required for triacylglycerol production in mammary epithelium
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作者：Beigneux, Anne P. ; Vergnes, Laurent ; Qiao, Xin 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2006
卷号：47
期号：4
页码：734-744
DOI：10.1194/jlr.M500556-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：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 characterizedglycerolipid acyltransferases. Agpat6's closest family memberis another novel gene that we have provisionally designatedAgpat8. Both Agpat6 and Agpat8 are conserved from plants, nematodes,and flies to mammals. AGPAT6, which is predicted to containmultiple membrane-spanning helices, is found exclusively withinthe endoplasmic reticulum (ER) in mammalian cells. To gain insightsinto the in vivo importance of Agpat6, we used the Agpat6 EScell 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 phenotypesof Agpat6^–/– mice was a defect in lactation. Pupsnursed by Agpat6^–/– mothers die perinatally. Normally,Agpat6 is expressed at high levels in the mammary epitheliumof 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 wasa dramatic decrease in the size and number of lipid dropletswithin mammary epithelial cells and ducts. Also, the milk fromAgpat6^–/– mice was markedly depleted in diacylglycerolsand triacylglycerols. Thus, we identified a novel glycerolipidacyltransferase of the ER, AGPAT6, which is crucial for theproduction 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