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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • 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
External organisations
  • University of Washington
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • cDNA cloning, Chromosomal localization, Insulin-dependent diabetes, Islet cell antibodies
Original languageEnglish
Pages (from-to)8337-8341
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number19
Publication statusPublished - 1991 Oct 1
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes