{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:59:47Z","timestamp":1779256787951,"version":"3.51.4"},"reference-count":0,"publisher":"American Diabetes Association","issue":"3","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1994,3,1]]},"abstract":"<jats:p>The murine severe combined immunodeficiency (scid) mutation was used to assess whether the diabetogenic effects of multiple low-dose streptozocin (MD-STZ) administration required the presence of functional T-cells. An STZ dose as low as 30 mg\/kg body wt for 5 days induced hyperglycemia in young NOD\/Lt-+\/+ male mice, whereas a dose of 50 mg\/kg for 5 days was required to elicit comparable hyperglycemia in C.B.-17-+\/+ male mice. The greater NOD strain sensitivity was not a function of preexisting insulitis, because insulitis- and diabetes-free NOD male mice congenic for a diabetes-resistant major histocompatibility complex haplotype were equally susceptible to MD-STZ. This was confirmed in NOD-scid\/scid and C.B.-17-scid\/scid males. Both were completely insulitis-free, and despite the absence of functional T- cells and B-cells, both congenic stocks were as sensitive to MD-STZ as congenic +\/+ controls. Indeed, MD-STZ-induced hyperglycemia in NOD-scid\/scid male mice was significantly higher than in NOD\/Lt-+\/+ male mice. The NOD-scid\/scid mouse as a recipient of adoptively transferred splenocytes clearly delineated a distinct pathogenesis of spontaneous insulin-dependent diabetes mellitus (IDDM) versus MD-STZ-induced hyperglycemia. Splenocytes from spontaneously diabetic NOD\/Lt males, but not those from donors given MD-STZ, readily transferred IDDM, even when host beta-cells were sensitized by a single injection of STZ before adoptive transfer. We conclude that IDDM induced by MD-STZ is not mediated by T-cell- or B-cell-dependent autoimmune mechanisms in a fashion analogous to the spontaneous IDDM characteristic of NOD mice.<\/jats:p>","DOI":"10.2337\/diab.43.3.433","type":"journal-article","created":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T17:22:06Z","timestamp":1379611326000},"page":"433-440","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":36,"title":["Multiple Low-Dose Streptozocin\u2013induced Diabetes in NOD-<i>scid\/scid<\/i> Mice in the Absence of Functional Lymphocytes"],"prefix":"10.2337","volume":"43","author":[{"given":"Ivan C","family":"Gerling","sequence":"first","affiliation":[{"name":"Jackson Laboratory\u2008Bar Harbor, Maine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harley","family":"Friedman","sequence":"additional","affiliation":[{"name":"University of Massachusetts Medical School\u2008Worcester, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dale L","family":"Greiner","sequence":"additional","affiliation":[{"name":"University of Massachusetts Medical School\u2008Worcester, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard D","family":"Shultz","sequence":"additional","affiliation":[{"name":"Jackson Laboratory\u2008Bar Harbor, Maine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward H","family":"Leiter","sequence":"additional","affiliation":[{"name":"Jackson Laboratory\u2008Bar Harbor, Maine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/43\/3\/433\/360533\/43-3-433.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/43\/3\/433\/360533\/43-3-433.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:25:31Z","timestamp":1667406331000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/43\/3\/433\/8635\/Multiple-Low-Dose-Streptozocin-induced-Diabetes-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,3,1]]},"references-count":0,"journal-issue":{"issue":"3","published-print":{"date-parts":[[1994,3,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diab.43.3.433","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,3,1]]}}}