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

Karlsen, Allan E. ; Hagopian, William A. ; Grubin, Catherine E. ; Dube, Syamalima ; Disteche, Christine M. ; Adler, David A. ; Bärmeier, Heike ; Mathewes, Shannon ; Grant, Francis J. and Foster, Don , et al. (1991) In Proceedings of the National Academy of Sciences of the United States of America 88(19). p.8337-8341
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
cDNA cloning, Chromosomal localization, Insulin-dependent diabetes, Islet cell antibodies
in
Proceedings of the National Academy of Sciences of the United States of America
volume
88
issue
19
pages
5 pages
publisher
National Academy of Sciences
external identifiers
  • pmid:1924293
  • scopus:0026046093
ISSN
0027-8424
DOI
10.1073/pnas.88.19.8337
language
English
LU publication?
no
id
edc4fbc5-eed4-4fa0-a00c-14ee37c6f017
date added to LUP
2019-09-11 09:35:33
date last changed
2024-06-27 04:57:44
@article{edc4fbc5-eed4-4fa0-a00c-14ee37c6f017,
  abstract     = {{<p>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 &lt;65% identity to previously published, highly conserved GAD-1 brain sequences, which show &gt;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.</p>}},
  author       = {{Karlsen, Allan E. and Hagopian, William A. and Grubin, Catherine E. and Dube, Syamalima and Disteche, Christine M. and Adler, David A. and Bärmeier, Heike and Mathewes, Shannon and Grant, Francis J. and Foster, Don and Lernmark, Åke}},
  issn         = {{0027-8424}},
  keywords     = {{cDNA cloning; Chromosomal localization; Insulin-dependent diabetes; Islet cell antibodies}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{19}},
  pages        = {{8337--8341}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences of the United States of America}},
  title        = {{Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10}},
  url          = {{http://dx.doi.org/10.1073/pnas.88.19.8337}},
  doi          = {{10.1073/pnas.88.19.8337}},
  volume       = {{88}},
  year         = {{1991}},
}