Genetically programmed development of salivary gland abnormalities in the NOD (nonobese diabetic)-scid mouse in the absence of detectable lymphocytic infiltration: a potential trigger for sialoadenitis of NOD mice.
NOD (nonobese diabetic) mice develop chronic lymphocytic infiltrates of the salivary glands (sialoadenitis) that correlate with a temporal decline in saliva production. To differentiate autoimmune and nonautoimmune components in this decline, we evaluated glandular function in NOD-scid mice. Although saliva volumes and protein concentrations appeared normal, amylase and EGF activities declined 50 and 20%, respectively, in NOD-scid mice between 10 and 25 weeks of age. Salivary protein profiles on SDS-polyacrylamide gels showed a profound decline in two prominent proteins of 32 and 20 kDa, and the emergence of a new 27-kDa protein. All three proteins exhibited amino acid sequence homology to parotid 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 strains lacking autoimmune disease. Submandibular gland histology revealed selective loss of acinar tissue despite an absence of sialoadenitis. 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.
Robinson
C P
CP
Department of Pathology and Laboratory Medicine, University of Florida, Gainesville, 32610, USA.
Yamamoto
H
H
Peck
A B
AB
Humphreys-Beher
M G
MG
D000595:Amino Acid Sequence; D000681:Amylases / Q000378:metabolism; D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D016688:Mice, Inbred NOD / Q000235:genetics*; D016513:Mice, SCID; D008969:Molecular Sequence Data; D008970:Molecular Weight; D012469:Salivary Glands / Q000002:abnormalities*; D012471:Salivary Proteins and Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012793:Sialadenitis / Q000235:genetics*; D012859:Sjogren's Syndrome / Q000503:physiopathology; D013363:Submandibular Gland / Q000473:pathology
C511597:Bpifa2 protein, mouse; D012471:Salivary Proteins and Peptides; D000681:Amylases