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The Journal of Neuroscience, July 27, 2005, 25(30):6958-6961; doi:10.1523/JNEUROSCI.1058-05.2005
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Chromogranin A Deficiency in Transgenic Mice Leads to Aberrant Chromaffin Granule Biogenesis
Taeyoon Kim,1
Chun-fa Zhang,1
Ziqing Sun,2
Heling Wu,2 and
Y. Peng Loh1
1Section on Cellular Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, and 2College of Biology, Peking University, 100871 Beijing, China
The biogenesis of dense-core secretory granules (DCGs), organelles responsible for the storage and secretion of neurotransmitters and neuropeptides in chromaffin cells, is poorly understood. Chromogranin A (CgA), which binds catecholamines for storage in the lumen of chromaffin granules, has been shown to be involved in DCG biogenesis in neuroendocrine PC12 cells. Here, we report that downregulation of CgA expression in vivo by expressing antisense RNA against CgA in transgenic mice led to a significant reduction in DCG formation in adrenal chromaffin cells. The number of DCGs formed in CgA antisense transgenic mice was directly correlated with the amount of CgA present in adrenal medulla. In addition, DCGs showed an increase in size, with enlargement in the volume around the dense core, a phenomenon that occurs to maintain constant "free" catecholamine concentration in the lumen of these granules. The extent of DCG swelling was inversely correlated with the number of DCGs formed, as well as the amount of CgA present in the adrenal glands of CgA antisense transgenic mice. These data indicate an essential role of CgA in regulating chromaffin DCG biogenesis and catecholamine storage in vivo.
Key words: chromogranin A; dense-core; secretory granule; biogenesis; transgenic; chromaffin; catecholamine; adrenal medulla
Received March 18, 2005;
revised May 24, 2005;
accepted June 17, 2005.
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