Expression of GAD67 and Novel GAD67 Splice Variants During Human Fetal Pancreas Development

Abstract

Glutamic acid decarboxylase (GAD) is a major inhibitory neurotransmitter in the brain, which catalyses the reaction of L-glutamate to γ-aminobutyric acid. There are two isoforms of GAD, a 65-kDa form and a 67-kDa form, which are encoded by two different genes. As previous studies suggested a role for GAD67 splice variants during fetal pancreas development, we have investigated the mRNA expression of GAD67 and GAD67 splice variants in a series of 14 human fetal pancreases between 14 weeks gestation and term and in adult control pancreases by RT-PCR. In this study, we demonstrate mRNA expression of GAD67 and four GAD67 splice variants, including GAD25, in human fetal and adult specimens. Some of the splice variants, including various proportions of exon 7 or a new exon between exons 6 and 7, have not been described before in the human pancreas. We speculate that the expression of these GAD67 splice variants might be related to human fetal pancreas development.

Glutamic acid decarboxylase 1 alternative splicing isoforms: characterization, expression and quantification in the mouse brain

“…These isoforms are coding for the shorter GAD25-1 leading peptide. Similar short transcripts were identified in human adult and fetal pancreatic islet cells, testis and adrenal gland [ 22 , 23 , 32 ]. The length of these two isoforms is almost identical to the length of the mRNA transcripts detected by Szabo et al [ 19 ] on Northern blots.…”

“…Alternative splicing of GAD1 gene has been also described in human pancreatic islet cells, adrenal cortex and testis. Human alternatively spliced mRNA is shorter than the GAD1 mRNA and comprises only of the first seven exons of the human GAD1 gene, thus encoding a shorter 25-kDa protein [ 22 , 23 ]. In rat testis and other tissues four novel GAD1 mRNA isoforms synthetized by alternative splicing combined with the utilization of an intron located polyadenylation site and additional transcription start site located in Intron3 were recently described [ 24 , 25 ].…”