{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:20:51Z","timestamp":1791300051532,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,11,23]],"date-time":"2005-11-23T00:00:00Z","timestamp":1132704000000},"content-version":"vor","delay-in-days":4313,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1994,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The non\u2010obese di\u00e1betic (NOD) mouse strain provides a remarkable model for investigating the mechanisms of autoimmunity. Independent genetic analyses of this model have previously shown that chromosome 1\u2010linked loci were involved in the control of periinsulitis and sialitis on the one hand and of insulitis and diabetes on the other hand. In the present work, analysis of a [NOD \u00d7 (NOD \u00d7 C57BL\/6)F1] backcross progeny allowed us to clearly dissociate two genetic regions: one was associated with periinsulitis and mapped to the middle region of chromosome 1, in the vicinity of the <jats:italic>Bcl<\/jats:italic>\u20102 gene; the other was associated with insulitis and mapped to the proximal part of the chromosome. Three intermediate markers <jats:italic>D1Mit18, D1Mit5<\/jats:italic> and <jats:italic>D1Mit19<\/jats:italic> covering at least 25 centiMorgans between these two regions, were associated with neither periinsulitis nor insulitis. The role of the <jats:italic>Bcl<\/jats:italic>\u20102\u2010linked region in the immune anomalies of NOD mice was further investigated in a (NOD \u00d7 C57BL\/6)F2 cross where the <jats:italic>Bcl<\/jats:italic>\u20102<jats:sup>nod<\/jats:sup> haplotype was linked to elevated serum levels of IgG (<jats:italic>p<\/jats:italic> 0.0005). The middle region of chromosome 1 is, therefore, involved in the control of three phenotypes, including periinsulitis, sialitis and hyperIgG, pointing to <jats:italic>Bcl<\/jats:italic>\u20102 as a good candidate for a cause of the NOD mouse disease. Consistent with the anti\u2010apoptotic function of the <jats:italic>Bcl<\/jats:italic>\u20102 gene product, activated T lymphocytes from NOD mice showed a markedly increased resistance to induction of apoptosis following deprivation of interleukin\u20102 when compared to those from non\u2010autoimmune strains. After the recent observation of the <jats:italic>Fas<\/jats:italic> gene alterations in the <jats:italic>lpr<\/jats:italic> and <jats:italic>lpr<\/jats:italic><jats:sup>cg<\/jats:sup> mutations, these findings indicate that deregulation of lymphoid cell apoptosis may be a general pathogenetic mechanism in autoimmune diseases.<\/jats:p>","DOI":"10.1002\/eji.1830240217","type":"journal-article","created":{"date-parts":[[2007,3,1]],"date-time":"2007-03-01T20:37:00Z","timestamp":1172781420000},"page":"380-384","source":"Crossref","is-referenced-by-count":66,"title":["Genetic analysis of immune dysfunction in non\u2010obese diabetic (NOD) mice: Mapping of a susceptibility locus close to the <i>Bcl\u20102<\/i> gene correlates with increased resistance of NOD T cells to apoptosis induction"],"prefix":"10.1002","volume":"24","author":[{"given":"Henri\u2010Jean","family":"Garchon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010Jian","family":"Luan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Eloy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"B\u00e9dossa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Fran\u00e7ois","family":"Bach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,11,23]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1538\/expanim1978.34.4_425","volume":"34","author":"Makino S.","year":"1980","journal-title":"Exp. 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