Multiple low-dose streptozocin-induced diabetes in NOD-scid/scid mice in the absence of functional lymphocytes.
Blood-Glucose: me, Cell-Nucleus: pa, Diabetes-Mellitus-Experimental: bl, ci, Islets-of-Langerhans: pa, Male, Mice, Mice-Inbred-NOD, Mice-SCID, Spleen: cy, Streptozocin, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes: ph, tr
Diabetes 1994 Mar;43(3):433-40
DK27722/DK/NIDDK, DK36175/DK/NIDDK, AI30389/AI/NIAID
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.
Gerling, I C.; Friedman, H; Greiner, D L.; Shultz, L D.; and Leiter, E H., " Multiple low-dose streptozocin-induced diabetes in NOD-scid/scid mice in the absence of functional lymphocytes." (1994). Faculty Research 1990 - 1999. 502.