Molecular cloning of full-length glutamic acid decarboxylase 67 from human pancreas and islets

Glutamic acid decarboxylase (GAD) is a pancreatic islet autoantigen in insulin-dependent diabetes (IDD). Two forms of GAD, GAD65 and GAD67, have been identified in brain but human islets have been reported to express only GAD65. We have isolated full length GAD67 cDNA by polymerase chain reaction (PCR) cloning from human pancreas. Sequence analysis reveals only four nucleotide differences between human pancreas and brain GAD67, two of which result in amino acid changes. These differences are probably individual-specific and reflect allelic variation. Using mRNA from isolated human islets a partial sequence was obtained by PCR cloning that was identical to the midregion of pancreas GAD67 cDNA. GAD67 has previously been shown to be a target of both autoantibodies and autoreactive T cells in IDD. The presence of GAD67 in human pancreas implies that this form of GAD, as well as GAD65, has a pathogenic role in IDD.