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Published online before print September 6, 2007
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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.070388

Accepted for publication June 26, 2007.

Article

Autoimmune Dacryoadenitis of NOD/LtJ Mice and Its Subsequent Effects on Tear Protein Composition

Máire E. Doyle*{dagger}@, Lori Boggs*, Robert Attia*, Lauren R. Cooper*, Daniel R. Saban*, Cuong Q. Nguyen*, and Ammon B. Peck*{dagger}{ddagger}

From the Department of Oral Biology,* and the Center for Orphan Autoimmune Diseases,{ddagger} College of Dentistry, and the Department of Pathology, Immunology, and Laboratory Medicine,{dagger} College of Medicine, University of Florida, Gainesville, Florida

@ To whom correspondence should be addressed. E-mail: mdoyle1{at}jhmi.edu.


  Abstract

Sjögren's syndrome (SjS) is a human autoimmune disease characterized by exocrine dysfunction resulting from chronic autoimmune attack primarily against the lacrimal and/or salivary glands. Although, we previously established a good correlation between SjS in humans and autoimmune exocrinopathy in NOD/LtJ mice an in-depth evaluation of lacrimal gland disease in the NOD/LtJ mouse has remained limited. This leaves a major gap in our understanding of the dacryoadenitis/keratoconjunctivitis sicca in this model. Here we characterize the development of the autoimmune dacryoadenitis in NOD/LtJ and NOD.B10-H2b mice in comparison with age- and sex-matched nonautoimmune CD1 mice. We observed a decline in tear production beginning at 8 weeks of age in both NOD/LtJ and NOD.B10-H2b mice, continuing throughout the 40 to 46 weeks studied. This correlated with a quantifiable increase in mixed T- and B-lymphocyte infiltrations in the extraorbital lacrimal glands. In addition, temporal differences in tear protein expression between NOD/LtJ and CD1 mice were identified using two-dimensional gel electrophoresis and tandem mass spectrometry. Thus, using this model we can identify potentially important pathophysiological mechanisms of the autoimmune attack and possible diagnostic markers for development of SjS-associated dacryoadenitis.






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Copyright © 2007 by the American Society for Investigative Pathology.