Increased expression of sulfated gp300 and acinar tissue pathology in
pancreas of cftr(-/-) mice.
De, Robert C., Lisle.
Department of Anatomy and Cell Biology, University of Kansas Medical
Center, Kansas City, KS 66160,
APStracts 2:0001G, 1995.
The CFTR(-/-) mouse model of cystic fibrosis (CF) has revealed that the mouse
pancreatic duct has a Ca2+-regulated chloride conductance which allows ductal
electrolyte transport to remain unaffected by loss of 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 post
-translational 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.
Received 29 September 1994; accepted in final form 6 January 1995.
APS Manuscript Number G384-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 February 1995