Alternative splicing of GAD67 results in the synthesis of a third form of glutamic-acid decarboxylase in human islets and other non-neural tissues

Two forms of glutamic-acid decarboxylase (GAD) have been identified in mamm alian tissues: a 65-kDa form (GAD65) and a 67-kDa form (GAD67). Alternate s plicing produces one or two smaller variants of GAD67 in the brain of embry onic mice and rats. Additionally, a short, heretofore unidentified transcri pt homologous to GAD67 has been detected in human testis RNA. Because GAD, the enzyme responsible for gamma-aminobutyric acid production and a key aut oantigen in type I diabetes, has unclear function in non-neural tissue, it is important to understand its pattern of expression. Unlike GAD65, GAD67 i s 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 dir ects the synthesis of a protein without GAD enzymatic activity: GAD25. A un ique peptide sequence at the carboxyl terminus of GAD25 is highly conserved between mice, rats, and humans. We conclude that humans produce a third fo rm of GAD in non-neural tissues and that human islets, although they do not synthesize full-length GAD67, do express this shortened variant.