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

Ivan Gerling, Harley Friedman, Dale L. Greiner, Leonard D. Shultz, Edward H. Leiter

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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 β-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.

Original languageEnglish (US)
Pages (from-to)433-440
Number of pages8
JournalDiabetes
Volume43
Issue number3
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

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Severe Combined Immunodeficiency
Experimental Diabetes Mellitus
Lymphocytes
Streptozocin
Type 1 Diabetes Mellitus
Hyperglycemia
Inbred NOD Mouse
T-Lymphocytes
B-Lymphocytes
Adoptive Transfer
Major Histocompatibility Complex
Haplotypes
Mutation
Injections

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Multiple low-dose streptozocin-induced diabetes in NOD-scid/scid mice in the absence of functional lymphocytes. / Gerling, Ivan; Friedman, Harley; Greiner, Dale L.; Shultz, Leonard D.; Leiter, Edward H.

In: Diabetes, Vol. 43, No. 3, 01.01.1994, p. 433-440.

Research output: Contribution to journalArticle

Gerling, Ivan ; Friedman, Harley ; Greiner, Dale L. ; Shultz, Leonard D. ; Leiter, Edward H. / Multiple low-dose streptozocin-induced diabetes in NOD-scid/scid mice in the absence of functional lymphocytes. In: Diabetes. 1994 ; Vol. 43, No. 3. pp. 433-440.
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