Document 1185
 DOCN  M9591185
 TI    Very-low-dose streptozotocin induces diabetes in insulin promoter-mB7-1
       transgenic mice.
 DT    9509
 AU    Harlan DM; Barnett MA; Abe R; Pechhold K; Patterson NB; Gray GS; June
       CH; Immune Cell Biology Program, Naval Medical Research Institute,;
       Bethesda, Maryland 20889-5607, USA.
 SO    Diabetes. 1995 Jul;44(7):816-23. Unique Identifier : AIDSLINE
       MED/95309551
 AB    Transgenic mice that express mouse B7-1 (mB7-1, recently designated
       CD80) on their pancreatic beta-cells maintain normal islet architecture,
       have normal pancreatic insulin content, and only rarely spontaneously
       develop insulitis and diabetes. Nevertheless, these mice display an
       extreme sensitivity to streptozotocin (STZ)-induced diabetes. Female
       mice were administered two STZ doses intraperitoneally, 20 and 40 mg/kg
       body wt, each for five consecutive days. Nontransgenic but otherwise
       syngeneic mice responded to the STZ with a moderate diminution in
       pancreatic insulin content but not with persistent glycosuria. In
       striking contrast, STZ administered to transgenic mice resulted in a
       severe diminution of pancreatic insulin content and in diabetes.
       Notably, the lower STZ dose resulted in diabetes only after a prolonged
       (26- to 100-day) latency. STZ-induced diabetes appears to be T-cell
       dependent, since treatment with T-cell-depleting (and in particular CD8+
       subset-depleting) antibodies ameliorated the response. Anti-mB7-1
       monoclonal antibody administration also prevented STZ-induced diabetes.
       Thus, unmasked mB7-1 is a required component in the pathway resulting in
       beta-cell killing. Immunohistological analysis revealed that early after
       STZ administration, both mB7-1 transgenic and nontransgenic mice
       developed insulitis. While this insulitis resolved in the nontransgenic
       mice, the islet-infiltrating CD4+ and CD8+ T-cells in the transgenic
       mice were associated with complete beta-cell destruction. These data
       suggest that STZ-induced diabetes in mB7-1 transgenic mice is an
       immune-mediated process with distinct potential advantages over existing
       insulin-dependent diabetes models.
 DE    Animal  Antibodies/PHARMACOLOGY  B-Cell Activation
       Antigen/*BIOSYNTHESIS/GENETICS  Blood Glucose/METABOLISM  Comparative
       Study  CD8-Positive T-Lymphocytes/IMMUNOLOGY  Diabetes Mellitus,
       Experimental/IMMUNOLOGY/PATHOLOGY/  *PHYSIOPATHOLOGY  Disease
       Susceptibility  Dose-Response Relationship, Drug  Drug Administration
       Schedule  Female  Glycosuria  Insulin/ANALYSIS/*GENETICS  Islets of
       Langerhans/IMMUNOLOGY/*PATHOLOGY  Lymphocyte Depletion  Mice  Mice,
       Transgenic  *Promoter Regions (Genetics)  Streptozocin/ADMINISTRATION &
       DOSAGE/*TOXICITY  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       Non-P.H.S.  T-Lymphocytes/IMMUNOLOGY  Time Factors  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).