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Åke Lernmark

Principal investigator

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Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10

Author

  • Allan E. Karlsen
  • William A. Hagopian
  • Catherine E. Grubin
  • Syamalima Dube
  • Christine M. Disteche
  • David A. Adler
  • Heike Bärmeier
  • Shannon Mathewes
  • Francis J. Grant
  • Don Foster
  • Åke Lernmark

Summary, in English

Glutamic acid decarboxylase (GAD; glutamate decarboxylase, L-glutamate 1-carboxy-lyase, EC 4.1.1.15), which catalyzes formation of γ-aminobutyric acid from L-glutamic acid, is detectable in different isoforms with distinct electrophoretic and kinetic characteristics. GAD has also been implicated as an autoantigen in the vastly differing autoimmune disease stiff-man syndrome and insulin-dependent diabetes mellitus. Despite the differing GAD isoforms, only one type of GAD cDNA (GAD-1), localized to a syntenic region of chromosome 2, has been isolated from rat, mouse, and cat. Using sequence information from GAD-1 to screen a human pancreatic islet cDNA library, we describe the isolation of an additional GAD cDNA (GAD-2), which was mapped to the short arm of human chromosome 10. Genomic Southern blotting with GAD-2 demonstrated a hybridization pattern different from that detected by GAD-1. GAD-2 recognizes a 5.6-kilobase transcript in both islets and brain, in contrast to GAD-1, which detects a 3.7-kilobase transcript in brain only. The deduced 585-amino acid sequence coded for by GAD-2 shows <65% identity to previously published, highly conserved GAD-1 brain sequences, which show >96% deduced amino acid sequence homology among the three species. The fuction of this additional islet GAD isoform and its importance as an autoantigen in insulin-dependent diabetes remain to be determined.

Publishing year

1991-10-01

Language

English

Pages

8337-8341

Publication/Series

Proceedings of the National Academy of Sciences of the United States of America

Volume

88

Issue

19

Document type

Journal article

Publisher

National Acad Sciences

Topic

  • Cell and Molecular Biology

Keywords

  • cDNA cloning
  • Chromosomal localization
  • Insulin-dependent diabetes
  • Islet cell antibodies

Status

Published

ISBN/ISSN/Other

  • ISSN: 0027-8424