Differential Expression of GAD65 and GAD67 in Human, Rat, and Mouse Pancreatic Islets
Open accessAbstract
The smaller form of the autoantigen glutamic acid decarboxylase, GAD65 (formerly the 64,000 M(r) autoantigen), is a major target of humoral autoimmunity in type I diabetes. Human autoantisera have been used extensively to characterize the GAD65 antigen in both rat and human islets, but the protein has escaped detection in mouse islets. We have now analyzed the expression of GAD65 and GAD67, the larger glutamic acid decarboxylase protein, in human, rat, and mouse islets of Langerhans and brain, using human monoclonal islet cell autoantibodies, human autoantisera, and experimentally raised antibodies to glutamic acid decarboxylase. Human monoclonal autoantibodies and experimentally raised antibodies reacted with mouse GAD65 produced in a baculovirus expression system by Western blotting and immunoprecipitation and with GAD65 in mouse brain by immunohistochemistry but failed to detect GAD65 in mouse islets by the latter two methods. However, analysis of mouse islets by Western blotting technique, using the most sensitive experimentally raised antibody, showed that mouse islets express both GAD65 and GAD67 but at levels that are severalfold lower than those in mouse brain or in human and rat islets. Furthermore, both human and rat islets predominantly express GAD65, whereas GAD67 is the major glutamic acid decarboxylase protein in mouse islets. Human islets are significantly distinct from mouse and rat islets and from brain because they only express GAD65, which is consistent wit…
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Mouse islets express Gad1 (GAD65) whereas GAD2 (GAD67) is found in human β-cells.
“Mouse islets express Gad1 (GAD65) whereas GAD2 (GAD67) is found in human β-cells (348).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [348]
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- Authors
- Kim, J., Richter, W., Aanstoot, H.-J., Shi, Y., Fu, Q., Rajotte, R., Warnock, G., & Baekkeskov, S.
- Affiliations
- University of Alberta (CA)
- Department of Medicine and the Department of Microbiology and Immunology, Hormone Research Institute, University of California at San Francisco San Francisco, California Surgical Medical Research Institute, University of Alberta Edmonton, Canada
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1993-12-01
- Volume
- 42
- Issue
- 12
- Pages
- 1799-1808
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2129973402
- Cited by
- 176
- References
- 0
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 5 · 2013: 6 · 2012: 7
- FWCI
- 6.49
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (5p01dk041822-10)
- National Institute of Diabetes and Digestive and Kidney Diseases (1PO1-DK-41822)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- GAD65, GAD67, glutamic acid decarboxylase, pancreatic islets, type 1 diabetes, autoantigens, islet autoantibodies, islet autoimmunity, species differences, mouse islets, rat islets, human islets, brain
- MeSH terms
- Amino Acid Sequence, Animals, Antibodies, Monoclonal, Autoantibodies, Autoantigens, Brain, Cell Line, Female, Glutamate Decarboxylase, Humans, Immunohistochemistry, Islets of Langerhans, Isoenzymes, Mice, Inbred Strains, Molecular Sequence Data, Moths, Recombinant Proteins, Transfection, Blotting, Western, Gene Expression, Mice, Inbred NOD, Rats, Wistar, Sequence Homology, Amino Acid, Mice, Rats
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