{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:22:49Z","timestamp":1790965369378,"version":"4.1.0"},"reference-count":12,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2001,1,1]],"date-time":"2001-01-01T00:00:00Z","timestamp":978307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2001,1,1]],"date-time":"2001-01-01T00:00:00Z","timestamp":978307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Immunogenet"],"published-print":{"date-parts":[[2001]]},"abstract":"<i>Objectives:<\/i> 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. <i>Methods:<\/i> Submandibular glands were removed for histological, immunohistochemical and biochemical evaluation from neonatal NOD and congenic strains as well as healthy control C57BL\/6 mice. <i>Results:<\/i> 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 (<i>Idd3<\/i> and <i>Idd5<\/i>) in NOD mice resulted in an hierarchical and additive reversal of delayed organogenesis, elevated MMP-9 activity, and aberrant expression of parotid secretory protein. <i>Discussion:<\/i> 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.<\/jats:p>","DOI":"10.1159\/000049194","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T10:10:37Z","timestamp":1050401437000},"page":"143-160","source":"Crossref","is-referenced-by-count":43,"title":["Abnormal Organogenesis in Salivary Gland Development May Initiate Adult Onset of Autoimmune Exocrinopathy"],"prefix":"10.1159","volume":"18","author":[{"given":"Seunghee","family":"Cha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia C.A.","family":"van Blockland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan A.","family":"Versnel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Homo-Delarche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Nagashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Brayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammon B.","family":"Peck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Humphreys-Beher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2001,9,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.30.20745"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199801)41:1<150::AID-ART18>3.3.CO;2-K"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1993.1137"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.11.5767"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5312.604"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1007\/s003359900097"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90233-9"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(98)90086-5"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.10.6594"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038\/346281a0"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199705)171:2<117::AID-JCP1>3.0.CO;2-R"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5430.1028"}],"container-title":["Experimental and Clinical Immunogenetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/49194","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/49194","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:12:25Z","timestamp":1745467945000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000049194"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001]]},"references-count":12,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2001,9,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000049194","archive":["Portico"],"relation":{},"ISSN":["0254-9670","1421-9948"],"issn-type":[{"value":"0254-9670","type":"print"},{"value":"1421-9948","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001]]}}}