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Sensitivity of the brain transcriptome to connexin ablation
Dumitru A Iacobas1, Sanda Iacobas, Marcia Urban-Maldonado
1Department of Neuroscience, Albert Einstein College of Medicine, 1410 Pelham Parkway South, Kennedy Center, Room 915C, New York, NY 10461, United States. diacobas@aecom.yu.edu
Biochimica Et Biophysica Acta
|June 16, 2005
Summary
Connexin expression, like connexin43 (Cx43) and connexin32 (Cx32), significantly impacts gene regulation in mouse brains. This suggests connexins act as a central regulator for brain gene expression patterns.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Previous studies on connexin43 (Cx43) and connexin32 (Cx32) disruptions in mice showed minimal central nervous system changes.
- Connexins are crucial for cell-to-cell communication, but their broader role in gene regulation is not fully understood.
Purpose of the Study:
- To investigate the global gene expression changes in mouse brains with altered connexin43 (Cx43) and connexin32 (Cx32) levels.
- To identify specific genes and pathways regulated by connexin expression in the brain.
Main Methods:
- Utilized high-density cDNA arrays to analyze transcriptomes of 7446 genes in Cx43 null, Cx43 heterozygous, and Cx32 null mouse brains compared to wildtype.
- Employed multiple samples for robust statistical determination of gene regulation significance.
Main Results:
- Identified significant regulation of genes across all functional categories, extending beyond expected junctional communication roles.
- Observed high similarity in gene regulation between Cx43 null and heterozygous models, and a notable overlap between Cx43 null and Cx32 null models.
- Demonstrated an inverse correlation between regulated genes in Cx43-altered brains and Cx43 expression levels in wildtype brains, suggesting predictability.
Conclusions:
- Connexin expression levels are strongly linked to widespread gene expression patterns in the brain.
- Connexins may serve as a central regulatory node controlling gene expression in the central nervous system.