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

作者：Allan Ertmann Karlsen, William Hagopian, Catherine E. Grubin, Syamalima Dube, Christine M. Distèche, David A. Adler, Heike Bärmeier, Shannon L. Mathewes, Francis James Grant, Donald C. Foster · 发表于：Proceedings of the National Academy of Sciences · 年份：1991 · DOI：10.1073/pnas.88.19.8337 · 被引用次数：282 · 研究领域：Diabetes and associated disorders、Pancreatic function and diabetes、Diet, Metabolism, and Disease

Glutamic acid decarboxylase (GAD; glutamate decarboxylase, L-glutamate 1-carboxy-lyase, EC 4.1.1.15), which catalyzes formation of gamma-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 less than 65% identity to previously published, highly conserved GAD-1 brain sequences, which show greater than 96% deduced amino acid sequence homology among the three species. The function of this additional islet GAD isoform and its importance as an autoantigen in insulin-dependent diabetes remain to be determined.