title: Autoimmune dacryoadenitis of NOD/LtJ mice and its subsequent effects on tear protein composition.
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-H2(b) 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-H2(b) 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.
authors.affiliation: Department of Oral Biology, College of Medicine, University of Florida, Gainesville, Florida, USA. mdoyle1@jhmi.edu
authors.forename: Máire E
authors.initials: ME
authors.lastname: Doyle
authors.forename: Lori
authors.initials: L
authors.lastname: Boggs
authors.forename: Robert
authors.initials: R
authors.lastname: Attia
authors.forename: Lauren R
authors.initials: LR
authors.lastname: Cooper
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Saban
authors.forename: Cuong Q
authors.initials: CQ
authors.lastname: Nguyen
authors.forename: Ammon B
authors.initials: AB
authors.lastname: Peck
mesh_terms: D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology; D003607:Dacryocystitis / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D005136:Eye Proteins / Q000032:analysis*; D005260:Female; D007638:Keratoconjunctivitis Sicca / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D007765:Lacrimal Apparatus / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D012737:Sex Factors; D013601:T-Lymphocytes / Q000276:immunology; D053719:Tandem Mass Spectrometry; D013666:Tears / Q000737:chemistry* / Q000378:metabolism