Diabetes, Vol 43, Issue 3 433-440, Copyright © 1994 by American Diabetes Association

ARTICLES

Multiple low-dose streptozocin-induced diabetes in NOD-scid/scid mice in the absence of functional lymphocytes

IC Gerling, H Friedman, DL Greiner, LD Shultz and EH Leiter
Jackson Laboratory, Bar Harbor, ME 04609.

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.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. C. Barlow, W. Langston, K. M. Matthews, J. H. Chidlow Jr, and C. G. Kevil CD18 Deficiency Protects against Multiple Low-Dose Streptozotocin-Induced Diabetes Am. J. Pathol., December 1, 2004; 165(6): 1849 - 1852. [Abstract] [Full Text] [PDF]

				W. H. Schott, B. D. Haskell, H. M. Tse, M. J. Milton, J. D. Piganelli, C. M. Choisy-Rossi, P. C. Reifsnyder, A. V. Chervonsky, and E. H. Leiter Caspase-1 Is Not Required for Type 1 Diabetes in the NOD Mouse Diabetes, January 1, 2004; 53(1): 99 - 104. [Abstract] [Full Text] [PDF]

				S. Bertera, M. L. Crawford, A. M. Alexander, G. D. Papworth, S. C. Watkins, P. D. Robbins, and M. Trucco Gene Transfer of Manganese Superoxide Dismutase Extends Islet Graft Function in a Mouse Model of Autoimmune Diabetes Diabetes, February 1, 2003; 52(2): 387 - 393. [Abstract] [Full Text] [PDF]

				L. Yang, S. Li, H. Hatch, K. Ahrens, J. G. Cornelius, B. E. Petersen, and A. B. Peck In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone-producing cells PNAS, May 30, 2002; (2002) 122210699. [Abstract] [Full Text] [PDF]

				C. Gonzalez, J. Menissier de Murcia, P. Janiak, J.-P. Bidouard, C. Beauvais, S. Karray, H.-J. Garchon, and M. Levi-Strauss Unexpected Sensitivity of Nonobese Diabetic Mice With a Disrupted Poly(ADP-Ribose) Polymerase-1 Gene to Streptozotocin-Induced and Spontaneous Diabetes Diabetes, May 1, 2002; 51(5): 1470 - 1476. [Abstract] [Full Text] [PDF]

				S. Lesage and C. C. Goodnow Organ-specific Autoimmune Disease: A Deficiency of Tolerogenic Stimulation J. Exp. Med., September 4, 2001; 194(5): F31 - F36. [Full Text] [PDF]

				M. Enghofer, J. Bojunga, R. Ludwig, A. Oldenburg, A. Bernd, K. H. Usadel, and K. Kusterer Lymphocyte transfer in streptozotocin-induced diabetes: adhesion of donor cells to islet endothelium Am J Physiol Endocrinol Metab, May 1, 1998; 274(5): E928 - E935. [Abstract] [Full Text] [PDF]