| First Author | Gerling IC | Year | 1994 |
| Journal | Diabetes | Volume | 43 |
| Issue | 3 | Pages | 433-40 |
| PubMed ID | 8314017 | Mgi Jnum | J:16998 |
| Mgi Id | MGI:65054 | Doi | 10.2337/diab.43.3.433 |
| Citation | Gerling IC, et al. (1994) Multiple low-dose streptozocin-induced diabetes in NOD-scid/scid mice in the absence of functional lymphocytes. Diabetes 43(3):433-40 |
| abstractText | 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. |
