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Ontogeny and tissue distribution of human GAD expression
M I Mally1, V Cirulli, T Otonkoski
1Whittier Institute, Department of Pediatrics, University of California, San Diego, School of Medicine, La Jolla, 92037, USA.
Diabetes
|April 1, 1996
Summary
Glutamate decarboxylase (GAD) gene expression, particularly GAD65, is present in the developing human pancreas, suggesting a role in islet development. GAD65 may serve as a marker for primitive islet cells.
Area of Science:
- Endocrinology
- Developmental Biology
- Neuroscience
Background:
- Glutamate decarboxylase (GAD) is a key autoantigen in Type 1 Diabetes (T1D).
- GAD expression is known in adult pancreatic islets, but its developmental expression in the human pancreas is uncharacterized.
- GAD exists in two isoforms: GAD65 and GAD67.
Purpose of the Study:
- To investigate the transcriptional expression patterns of GAD65 and GAD67 during human pancreatic ontogeny.
- To determine the tissue-specific expression of GAD genes.
- To explore the potential role of GAD65 in early islet development and cell identification.
Main Methods:
- Quantitative analysis of GAD65 and GAD67 mRNA in human fetal, postnatal, and adult pancreases, and isolated adult islets.
- Tissue-specific expression analysis.
- Triple immunofluorescent staining to examine GAD65 colocalization with pancreatic cell markers (insulin, glucagon) and its presence in epithelial and ductal cells.
Main Results:
- Significant GAD65 transcripts were detected from 13 weeks of gestation, with higher levels in fetal and infantile pancreases compared to adults.
- Isolated adult islets showed high enrichment of GAD65 mRNA.
- GAD67 transcripts were undetectable in fetal and postnatal pancreases, but GAD65 was highly expressed in the brain and pancreas, with minimal expression in other tissues.
- GAD65 colocalized with alpha- and beta-cells in both fetal and adult pancreases.
- Fetal pancreatic epithelial cells, including ductal cells lacking insulin/glucagon, showed strong GAD65 immunoreactivity.
Conclusions:
- This study provides the first evidence of GAD65 expression in the human fetal pancreas, indicating a potential role in human islet development.
- GAD65 expression in early pancreatic cells suggests it could be a valuable marker for identifying primitive islet cells.
- The distinct expression patterns of GAD65 and GAD67 during pancreatic development warrant further investigation into their specific roles.