AJP - Gastrointestinal and Liver Physiology, Vol 268, Issue 4 717-G723, Copyright © 1995 by American Physiological Society

ARTICLES

Increased expression of sulfated gp300 and acinar tissue pathology in pancreas of CFTR(-/-) mice

R. C. De Lisle
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City 66160, USA.

The CFTR (-/-) mouse model of cystic fibrosis (CF) has revealed that the mouse pancreatic duct has a Ca(2+)-regulated chloride conductance that allows ductal electrolyte transport to remain unaffected by loss of the cystic fibrosis transmembrane conductance regulator (CFTR). Therefore, this model provides a unique opportunity to investigate effects of CF on the acinar tissue. It has been reported that exocrine secretions contain higher levels of sulfate in CF. We discovered in CFTR(-/-) acini that gp300, the major sulfated glycoprotein of the mouse acinar cell, has increased steady-state and biosynthetic levels. However, there are no apparent changes in sulfate or carbohydrate composition of gp300, indicating that posttranslational processing of this sulfated glycoprotein is not altered in CF. In addition to the increase in gp300, the morphology of CF acinar tissue is dramatically altered: acinar lumina of CFTR(-/-) mice are greatly dilated and filled with aggregated protein. gp300, which in the normal tissue is mainly localized to the zymogen granule membrane, was found to line the distended luminal membranes in the CF tissue. These results demonstrate that the acinar tissue is affected in the CF mouse and that expression of the major sulfated glycoprotein is also increased. It is suggested that increased expression of gp300 in CFTR(-/-) mice may cause poorly soluble exocrine protein secretion, contributing to the development of CF in the pancreas.

This article has been cited by other articles:

				S. Kaur, O. Norkina, D. Ziemer, L. C. Samuelson, and R. C. De Lisle Acidic duodenal pH alters gene expression in the cystic fibrosis mouse pancreas Am J Physiol Gastrointest Liver Physiol, August 1, 2004; 287(2): G480 - G490. [Abstract] [Full Text] [PDF]

				R. C. De Lisle, K. S. Isom, D. Ziemer, and C. U. Cotton Changes in the exocrine pancreas secondary to altered small intestinal function in the CF mouse Am J Physiol Gastrointest Liver Physiol, October 1, 2001; 281(4): G899 - G906. [Abstract] [Full Text] [PDF]

				B. R. GRUBB and R. C. BOUCHER Pathophysiology of Gene-Targeted Mouse Models for Cystic Fibrosis Physiol Rev, January 1, 1999; 79(1): 193 - 214. [Abstract] [Full Text] [PDF]

				N. Sharer, M. Schwarz, G. Malone, A. Howarth, J. Painter, M. Super, and J. Braganza Mutations of the Cystic Fibrosis Gene in Patients with Chronic Pancreatitis N. Engl. J. Med., September 3, 1998; 339(10): 645 - 652. [Abstract] [Full Text] [PDF]

				R. C. De Lisle, M. Petitt, K. S. Isom, and D. Ziemer Developmental expression of a mucinlike glycoprotein (MUCLIN) in pancreas and small intestine of CF mice Am J Physiol Gastrointest Liver Physiol, August 1, 1998; 275(2): G219 - G227. [Abstract] [Full Text] [PDF]