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Diacylglycerol o-acyltransferase 2alpha (DGAT2alpha)

a technology of acylglycerol and acyltransferase, applied in the field of acyltransferases, can solve the problem of reducing the period of time that the therapy is effectiv

Inactive Publication Date: 2002-08-29
RGT UNIV OF CALIFORNIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

An immune response of a recipient against the blocking agent will potentially decrease the period of time that the therapy is effective.

Method used

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  • Diacylglycerol o-acyltransferase 2alpha (DGAT2alpha)
  • Diacylglycerol o-acyltransferase 2alpha (DGAT2alpha)
  • Diacylglycerol o-acyltransferase 2alpha (DGAT2alpha)

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Experimental program
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Embodiment Construction

[0129] I. Existence of DGAT2.alpha.

[0130] A. Mice (DGAT1- / -) lacking DGAT, as described in WO 99 / 67268 are lean and resistant to diet-induced obesity, but are still capable of synthesizing triglycerides (TG) and have normal plasma TG levels. However, DGAT activity is virtually absent in membrane preparations from DGAT1- / - tissues (Smith et al., Nat. Genet. 2000 (25), 87-90). Using pulse assays in living cells, we measured that the residual TG synthesis activity in DGAT 1- / -Mouse Embryonic Fibroblasts (MEF) or adipocytes was about 40% of that in wild-type cells. The results are graphically depicted in FIGS. 1A and 1B. In FIG. 1A the membrane fraction isolated from MEF or adipocytes of wild-type or DGAT1- / - mice was used as the enzyme source in DGAT assays in vitro. In FIH. 1B living cells were pulse-labeled with [.sup.14C]oleic acid for 24 hours and [.sup.14C] incorporation in the TG fraction was measured.

[0131] In further assays, increased DGAT activity was observed in DGAT.sup.-1-m...

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Abstract

Nucleic acid compositions encoding mammalian DGAT2alpha polypeptide products with diglyceride acyltransferase activity, as well as the mammalian DGAT2alpha polypeptide products encoded thereby and methods for producing the same, are provided. The subject DGAT2alpha polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications, as well as in treatment therapies and in the production of triacylglycerols.

Description

[0001] Pursuant to 35 U.S.C. .sctn. 119(e), this application claims priority to the filing date of the U.S. Provisional Patent Application Serial No. 60 / ______ filed Feb. 23, 2001 and bearing the title "DIACYLGLYCEROL O-ACYLTRANSFERASE 2.alpha. (DGAT2.alpha.) (Attorney Docket No. 6510-240PRV), the disclosure of which is herein incorporated by reference.[0002] 1. Field of the Invention[0003] The field of the invention is enzymes, particularly acyltransferases. Background of the Invention Diacylglycerol O-Acyltransferase (EC 2.3.1.20), also known as diglyceride acyltransferase or DGAT, is a critical enzyme in triacylglycerol synthesis. Triacylglycerols are quantitatively the most important storage form of energy for eukaryotic cells. DGAT catalyzes the rate-limiting and terminal step in triacylglycerol synthesis using diacylglycerol and fatty acyl CoA as substrates. As such, DGAT plays a fundamental role in the metabolism of cellular diacylglycerol and is important in higher eukaryote...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/00C12N9/10
CPCA01K2217/05A61K38/00A61K2039/505C12N9/1029C12Y203/0102C12Y203/01022
Inventor CASES, SYLVAINEFARESE, ROBERT V.STONE, SCOTZHOU, PING
Owner RGT UNIV OF CALIFORNIA
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