This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hendy, G. N. Articles by Canaff, L. Search for Related Content PubMed PubMed Citation Articles by Hendy, G. N. Articles by Canaff, L.

Targeted Ablation of the Chromogranin A (Chga) Gene: Normal Neuroendocrine Dense-Core Secretory Granules and Increased Expression of Other Granins

Departments of Medicine (G.N.H., T.L., M.G., R.C.F., S.M., A.C.K., L.C.), Physiology (G.N.H., S.M.), Human Genetics (G.N.H., A.C.K.), Biochemistry (M.L.T.), and McGill Cancer Centre (M.L.T.), McGill University and Calcium Research Laboratory (G.N.H., L.C.), and Hormones and Cancer Research Unit (G.N.H.), Royal Victoria Hospital, Montreal, Québec, Canada H3A 1A1; and Département de Pharmacologie (R.De., R.Da.), Faculté de Médicine et Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Québec, Canada J1H 5N5

Address all correspondence and requests for reprints to: Dr. Geoffrey N. Hendy, Calcium Research Laboratory, Royal Victoria Hospital, 687 Pine Avenue West, Room H4.67, Montreal, Québec, Canada H3A 1A1. E-mail: geoffrey.hendy{at}mcgill.ca.

Chromogranin A (CgA), originally identified in adrenal chromaffin cells, is a member of the granin family of acidic secretory glycoproteins that are expressed in endocrine cells and neurons. CgA has been proposed to play multiple roles in the secretory process. Intracellularly, CgA may control secretory granule biogenesis and target neurotransmitters and peptide hormones to granules of the regulated pathway. Extracellularly, peptides formed as a result of proteolytic processing of CgA may regulate hormone secretion. To investigate the role of CgA in the whole animal, we created a mouse mutant null for the Chga gene. These mice are viable and fertile and have no obvious developmental abnormalities, and their neural and endocrine functions are not grossly impaired. Their adrenal glands were structurally unremarkable, and morphometric analyses of chromaffin cells showed vesicle size and number to be normal. However, the excretion of epinephrine, norepinephrine, and dopamine was significantly elevated in the Chga null mutants. Adrenal medullary mRNA and protein levels of other dense-core secretory granule proteins including chromogranin B, and secretogranins II to VI were up-regulated 2- to 3-fold in the Chga null mutant mice. Hence, the increased expression of the other granin family members is likely to compensate for the Chga deficiency.

This article has been cited by other articles:

				K. B. Helle The chromogranin A-derived peptides vasostatin-I and catestatin as regulatory peptides for cardiovascular functions Cardiovasc Res, August 18, 2009; (2009) cvp266v2. [Abstract] [Full Text] [PDF]

				M. Montero-Hadjadje, S. Elias, L. Chevalier, M. Benard, Y. Tanguy, V. Turquier, L. Galas, L. Yon, M. M. Malagon, A. Driouich, et al. Chromogranin A Promotes Peptide Hormone Sorting to Mobile Granules in Constitutively and Regulated Secreting Cells: ROLE OF CONSERVED N- AND C-TERMINAL PEPTIDES J. Biol. Chem., May 1, 2009; 284(18): 12420 - 12431. [Abstract] [Full Text] [PDF]

				P. Prasad, A. A. Yanagihara, A. L. Small-Howard, H. Turner, and A. J. Stokes Secretogranin III Directs Secretory Vesicle Biogenesis in Mast Cells in a Manner Dependent upon Interaction with Chromogranin A J. Immunol., October 1, 2008; 181(7): 5024 - 5034. [Abstract] [Full Text] [PDF]

				J. Xie, W.-Q. Wang, T.-X. Liu, M. Deng, and G. Ning Spatio-temporal expression of chromogranin A during zebrafish embryogenesis J. Endocrinol., September 1, 2008; 198(3): 451 - 458. [Abstract] [Full Text] [PDF]

				L. Han, M. Suda, K. Tsuzuki, R. Wang, Y. Ohe, H. Hirai, T. Watanabe, T. Takeuchi, and M. Hosaka A Large Form of Secretogranin III Functions as a Sorting Receptor for Chromogranin A Aggregates in PC12 Cells Mol. Endocrinol., August 1, 2008; 22(8): 1935 - 1949. [Abstract] [Full Text] [PDF]

				M. S. Montesinos, J. D. Machado, M. Camacho, J. Diaz, Y. G. Morales, D. Alvarez de la Rosa, E. Carmona, A. Castaneyra, O. H. Viveros, D. T. O'Connor, et al. The Crucial Role of Chromogranins in Storage and Exocytosis Revealed Using Chromaffin Cells from Chromogranin A Null Mouse J. Neurosci., March 26, 2008; 28(13): 3350 - 3358. [Abstract] [Full Text] [PDF]

				J. D. Dikeakos and T. L. Reudelhuber Sending proteins to dense core secretory granules: still a lot to sort out J. Cell Biol., April 23, 2007; 177(2): 191 - 196. [Abstract] [Full Text] [PDF]

				M. Courel, C. Rodemer, S. T. Nguyen, A. Pance, A. P. Jackson, D. T. O'Connor, and L. Taupenot Secretory Granule Biogenesis in Sympathoadrenal Cells: IDENTIFICATION OF A GRANULOGENIC DETERMINANT IN THE SECRETORY PROHORMONE CHROMOGRANIN A J. Biol. Chem., December 8, 2006; 281(49): 38038 - 38051. [Abstract] [Full Text] [PDF]