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J Biol Chem, Vol. 275, Issue 7, 5188-5192, February 18, 2000
From the Robert H. Williams Laboratory, Department of Medicine,
University of Washington, Seattle, Washington 98195-7710
Two forms of glutamic-acid decarboxylase (GAD)
have been identified in mammalian tissues: a 65-kDa form (GAD65) and a
67-kDa form (GAD67). Alternate splicing produces one or two smaller
variants of GAD67 in the brain of embryonic mice and rats.
Additionally, a short, heretofore unidentified transcript homologous to
GAD67 has been detected in human testis RNA. Because GAD, the enzyme responsible for The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF178853.
Alternative Splicing of GAD67 Results in the Synthesis of a Third
Form of Glutamic-acid Decarboxylase in Human Islets and Other
Non-neural Tissues*
and
-aminobutyric acid production and a key autoantigen in type I diabetes, has unclear function in non-neural tissue, it is
important to understand its pattern of expression. Unlike GAD65, GAD67
is not produced in human pancreatic islets. Here, we describe a novel
splice variant of GAD67 that is produced in human islets, testis,
adrenal cortex, and perhaps other endocrine tissues, but not in brain.
This transcript directs the synthesis of a protein without GAD
enzymatic activity: GAD25. A unique peptide sequence at the carboxyl
terminus of GAD25 is highly conserved between mice, rats, and humans.
We conclude that humans produce a third form of GAD in non-neural
tissues and that human islets, although they do not synthesize
full-length GAD67, do express this shortened variant.
*
This work was supported in part by National Institutes of
Health Grants DK26190 and DK53004 and by the Juvenile Diabetes
Foundation International Center of Excellence Program Project. Work
performed by Ben Snyder at the University of Washington Diabetes and
Endocrinology Research Center Molecular Biology Core was supported by
National Institutes of Health Grant DK17047. Work performed at the
Regional Primate Center of the University of Washington was supported
by National Institutes of Health Grant RR00166. Work performed at the
-Cell Transplant Central Unit was supported by a Shared Costs Action
of the European Community. Work performed at the Human Islet Isolation
and Cell Processing Facility, Puget Sound Blood Center/Northwest Tissue
Center, was supported in part by Howie funds from the University of
Washington and by facility development grant funds from the Virginia
Mason Research Center and Puget Sound Blood Center.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Fellow of the Juvenile Diabetes Foundation International. To whom
correspondence should be addressed: HSB, P. O. Box 357710, University
of Washington, Seattle, WA 98195-7710. Tel.: 206-221-4587; Fax:
206-543-3169; E-mail: chessler@u.washington.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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