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.

引用

页码：8754 / 8758

页数：5

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