CLONING, CHARACTERIZATION, AND AUTOIMMUNE RECOGNITION OF RAT ISLET GLUTAMIC-ACID DECARBOXYLASE IN INSULIN-DEPENDENT DIABETES-MELLITUS

被引：119
作者：
MICHELSEN, BK [1 ]
PETERSEN, JS [1 ]
BOEL, E [1 ]
MOLDRUP, A [1 ]
DYRBERG, T [1 ]
MADSEN, OD [1 ]
机构：
[1] NOVO NORDISK AS,DIABET RES,DK-2880 BAGSVAERD,DENMARK
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1991年 / 88卷 / 19期
关键词：
PARTIAL HUMAN INSULINOMA CDNA SEQUENCE; ALLELIC VARIATION; ALTERNATIVE MESSENGER RNA PROCESSING; EVOLUTION;
D O I：
10.1073/pnas.88.19.8754
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
A 64-kDa islet protein is a major autoantigen in insulin-dependent diabetes mellitus (IDDM). Autoantibodies against the 64-kDa protein were recently shown to immunoprecipitate glutamic acid decarboxylase (GAD; L-glutamate 1-carboxy-lyase, EC 4.1.1.15) from brain and from islets. We present evidence that the autoantisera also recognize a hydrophilic islet protein of almost-equal-to 67 kDa in addition to the amphiphilic 64-kDa form. We have isolated a full-length rat islet GAD cDNA encoding a hydrophilic 67-kDa protein, which appears to be identical to rat brain 67-kDa GAD. A partial sequence of human insulinoma 67-kDa GAD was identical to human brain 67-kDa GAD. Allelic variations were observed in rat as well as in human 67-kDa GAD sequences. The expressed rat islet 67-kDa GAD protein is functional and is immunoprecipitated by IDDM sera; it comigrates electrophoretically with the 67-kDa islet autoantigen. The hydrophilic 67-kDa form of GAD in islets is an additional autoantigen in IDDM and is recognized by a different subset of autoantibodies than the 64-kDa autoantigen. Thus, mammalian cell lines expressing functionally active, recombinant GAD may become important tools to study the nature and the role of GAD autoreactivity in IDDM.
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页码：8754 / 8758
页数：5
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