Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10
(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.
(Less)
- author
- publishing date
- 1991-10-01
- 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 <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.</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}}, }