help button home button Am J Pathol Epitomics, Inc.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Umans, L.
Right arrow Articles by Van Leuven, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Umans, L.
Right arrow Articles by Van Leuven, F.
(American Journal of Pathology. 1999;155:983-993.)
© 1999 American Society for Investigative Pathology

Animal Model

{alpha}2-Macroglobulin- and Murinoglobulin-1- Deficient Mice

A Mouse Model for Acute Pancreatitis

Lieve Umans, Lutgarde Serneels, Lut Overbergh, Lou Stas and Fred Van Leuven

From the Experimental Genetics Group, Center for Human Genetics, Flemish Institute for Biotechnology, Leuven, Belgium

Mice deficient in either or both mouse {alpha}2-macroglobulin (MAM) and murinoglobulin-1 (MUG1) were generated and proved phenotypically normal under standard conditions. Acute pancreatitis was induced with a diet deficient in choline and methionine, supplemented with ethionine. The mortality was less than 25% in wild-type mice, as opposed to at least 56% in knockout mice, and was highest (70%) in MAM-/- mice, with earliest onset at 2 days. Plasma amylase and lipase levels were increased, but pancreatic tissue appeared histologically variable in individual mice. The clinical symptoms were most severe in MAM-/- mice and, surprisingly, were not aggravated in the double knockout mice, suggesting that the lack of proteinase inhibition capacity was not the major problem. Therefore, we analyzed the expression of 21 different cytokines and polypeptide factors in the pancreas of all experimental groups of mice. Interleukin-1-receptor antagonist mRNA was consistently induced by the diet in the pancreas of MAM-/- mice, and transforming growth factor-ß, tumor necrosis factor-{alpha}, tumor necrosis factor-ß, ß-lymphotoxin, and interferon-{gamma} mRNA levels were also increased. The data demonstrate the important role of {alpha}2-macroglobulin (A2M) in acute pancreatitis as both a proteinase inhibitor and a cytokine carrier. Mice deficient in MAM and/or MUG thus offer new experimental models for defining in vivo the role of the macroglobulins in pancreatitis and in other normal and pathological processes.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
A. S. Kowalik, C. L. Johnson, S. A. Chadi, J. Y. Weston, E. N. Fazio, and C. L. Pin
Mice lacking the transcription factor Mist1 exhibit an altered stress response and increased sensitivity to caerulein-induced pancreatitis
Am J Physiol Gastrointest Liver Physiol, April 1, 2007; 292(4): G1123 - G1132.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C.-h. Wong, D. D. Mruk, M. K. Y. Siu, and C. Y. Cheng
Blood-Testis Barrier Dynamics Are Regulated by {alpha}2-Macroglobulin via the c-Jun N-Terminal Protein Kinase Pathway
Endocrinology, April 1, 2005; 146(4): 1893 - 1908.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
H. He, D. J. McCartney, Q. Wei, S. Esadeg, J. Zhang, R. A. Foster, M. A. Hayes, C. Tayade, F. Van Leuven, and B. A. Croy
Characterization of a Murine Alpha 2 Macroglobulin Gene Expressed in Reproductive and Cardiovascular Tissue
Biol Reprod, February 1, 2005; 72(2): 266 - 275.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
M. C. Waghabi, C. M. L. M. Coutinho, M. N. C. Soeiro, M. C. S. Pereira, J.-J. Feige, M. Keramidas, A. Cosson, P. Minoprio, F. Van Leuven, and T. C. Araujo-Jorge
Increased Trypanosoma cruzi Invasion and Heart Fibrosis Associated with High Transforming Growth Factor {beta} Levels in Mice Deficient in {alpha}2-Macroglobulin
Infect. Immun., September 1, 2002; 70(9): 5115 - 5123.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. V. Gourine, V. N. Gourine, Y. Tesfaigzi, N. Caluwaerts, F. Van Leuven, and M. J. Kluger
Role of alpha 2-macroglobulin in fever and cytokine responses induced by lipopolysaccharide in mice
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2002; 283(1): R218 - R226.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Kato, T. Kishi, T. Kamachi, M. Akisada, T. Oka, R. Midorikawa, K. Takio, N. Dohmae, P. I. Bird, J. Sun, et al.
Serine Proteinase Inhibitor 3 and Murinoglobulin I Are Potent Inhibitors of Neuropsin in Adult Mouse Brain
J. Biol. Chem., April 27, 2001; 276(18): 14562 - 14571.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1999 by the American Society for Investigative Pathology.