A novel NOD-derived murine model of primary Sjögren's syndrome.
OBJECTIVE
The appearance of autoimmune diabetes prior to autoimmune exocrinopathy in the NOD mouse suggests that it is an excellent model of secondary, but not primary, autoimmune sicca complications. Since the unique major histocompatibility complex (MHC) I-A(g7) expression in NOD mice is essential for the development of insulitis and diabetes in these animals, we investigated exocrine gland function in NOD.B10.H2b mice, which have an MHC congenic to NOD, as a potential model for primary Sjögren's syndrome (SS).


METHODS
Histopathologic manifestations of lymphocytic infiltrates into the pancreas and exocrine tissues were examined by light microscopy. Sera were evaluated for the presence of antinuclear antibodies. Saliva, tears, and gland lysates were evaluated for total volume and protein concentration, the aberrant expression and processing of parotid secretory protein, and cysteine protease activity.


RESULTS
NOD.B10.H2b mice exhibited the exocrine gland lymphocytic infiltration typical of the SS-like disease and dysfunction observed in NOD mice, but without the insulitis and diabetes. These mice additionally expressed elevated levels of cysteine protease activity (a measure of apoptotic activity) and abnormal expression and cleavage of parotid secretory protein in the submandibular tissues.


CONCLUSIONS
The results of this study suggest that the unique NOD MHC I-A(g7) is not essential for exocrine tissue autoimmunity. Furthermore, the findings indicate that sicca syndrome occurs independently of autoimmune diabetes and that the congenic NOD.B10.H2b mouse represents a novel murine model of primary SS.
Robinson
C P
CP
University of Florida, Gainesville 32610, USA.
Yamachika
S
S
Bounous
D I
DI
Brayer
J
J
Jonsson
R
R
Holmdahl
R
R
Peck
A B
AB
Humphreys-Beher
M G
MG
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007765:Lacrimal Apparatus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016296:Mutagenesis / Q000276:immunology; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology*; D013363:Submandibular Gland / Q000737:chemistry / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology
D015395:Histocompatibility Antigens Class I