Abnormal organogenesis in salivary gland development may initiate adult onset of autoimmune exocrinopathy.
OBJECTIVE
Salivary gland organogenesis was evaluated in NOD mice, an animal model for autoimmune exocrinopathy, to determine when disease onset is first present in the target tissues.


METHODS
Submandibular glands were removed for histological, immunohistochemical and biochemical evaluation from neonatal NOD and congenic strains as well as healthy control C57BL/6 mice.


RESULTS
Histomorphological analyses of neonatal submandibular glands, the primary target for autoimmune exocrinopathy at 1 day postpartum, revealed delayed morphological differentiation during organogenesis in autoimmune-susceptible NOD mice when compared to nonsusceptible C57BL/6 mice. Acinar cell proliferation was reduced, while expression of Fas, FasL and bcl-2 were increased. Acinar cell proliferation was reduced, while expression, of Fas, FasL and bcl-2 were increased. Throughout the preweaning period (21 days) submandibular glands from NOD and NOD congenic strains aberrantly expressed an increased matrix metalloproteinase (MMP)-2 and MMP-9 activity. Substitution of two susceptibility alleles (Idd3 and Idd5) in NOD mice resulted in an hierarchical and additive reversal of delayed organogenesis, elevated MMP-9 activity, and aberrant expression of parotid secretory protein.


CONCLUSIONS
NOD-derived mice whose submandibular glands showed normal organogenesis did not progress to develop autoimmune exocrinopathy. Altered organogenesis of target tissue may therefore provide a cellular microenvironment capable of activating autoimmunity.
Cha
S
S
Department of Oral Biology, University of Florida, Gainesville, FL 32610, USA.
van Blockland
S C
SC
Versnel
M A
MA
Homo-Delarche
F
F
Nagashima
H
H
Brayer
J
J
Peck
A B
AB
Humphreys-Beher
M G
MG
D000375:Aging / Q000276:immunology; D000483:Alleles; D000818:Animals; D020296:Animals, Congenic; D000831:Animals, Newborn; D017209:Apoptosis; D001327:Autoimmune Diseases / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D002455:Cell Division; D002874:Chromosome Mapping; D004847:Epithelial Cells / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D009024:Morphogenesis; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012859:Sjogren's Syndrome / Q000276:immunology / Q000503:physiopathology; D013363:Submandibular Gland / Q000201:enzymology / Q000254:growth & development* / Q000276:immunology / Q000473:pathology*
D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9