GENETICALLY PROGRAMMED DEVELOPMENT OF SALIVARY-GLAND ABNORMALITIES INTHE NOD (NONOBESE DIABETIC)-SCID MOUSE IN THE ABSENCE OF DETECTABLE LYMPHOCYTIC INFILTRATION - A POTENTIAL TRIGGER FOR SIALOADENITIS OF NODMICE

NOD (nonobese diabetic) mice develop chronic lymphocytic infiltrates o f the salivary glands (sialoadenitis) that correlate with a temporal d ecline in saliva production. To differentiate autoimmune and nonautoim mune components in this decline, we evaluated glandular function in NO D-scid mice. Although saliva volumes and protein concentrations appear ed normal, amylase and EGF activities declined 50 and 20%, respectivel y, in NOD-scid mice between 10 and 25 weeks of age. Salivary protein p rofiles on SDS-polyacrylamide gels showed a profound decline in two pr ominent proteins of 32 and 20 kDa, and the emergence of a new 27-kDa p rotein. All three proteins exhibited amino acid sequence homology to p arotid secretory protein (PSP) and reacted with PSP-specific antibody, suggesting an age-dependent alteration in PSP. In addition, there was an induced expression of proline-rich protein in the salivary glands and saliva of NOD and NOD-scid mice that was not detectable in mouse s trains lacking autoimmune disease. Submandibular gland histology revea led selective loss of acinar tissue despite an absence of sialoadeniti s. These changes in salivary protein composition and histology in the absence of detectable lymphocytic infiltration suggest that glandular defects in the NOD genetic background may contribute to the triggering of the autoimmune response in the salivary glands. (C) 1995 Academic Press, Inc.