Mouse Genome Informatics
tg1
    Tg(INS-MT2A,Tyr)1Pne/0
FVB-Tg(INS-MT2A,Tyr)1Pne
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• after a single dose of streptozocin, control animals become hyperglycemic (>400mg/dl) after 2 days, while transgenic animals do not acquire a similar degree of diabetes during the 6 days of observation
• islets from transgenic mice have 30-fold higher levels of metallothionein compared to control islets from FVB mice
• cultured transgenic islets are relatively protected from damage by streptozocin compared to control islets; control islets are visibly damaged by 0.25 mmol/l and disintegrate into single cells by 0.5 mmol/l streptozocin but transgenic islets don't exhibit a similar level of damage until exposure to a dose of 1 mmol/l
• transgenic islets have an increased threshold for DNA damage by streptozocin compared to control FVB islets

immune system
• transgenic islets transferred into streptozocin-induced diabetic BALB/c mice are able to maintain almost normal blood glucose levels for over 16 days in recipients, while control islets could maintain euglycemia for just over 8 days

endocrine/exocrine glands
• islets are resistant to morphological damage and cell death induced by incubation with SNAP, a nitric oxide donor; FVB control islets are damaged under the same conditions
• after transplantation of transgenic islet or control iset grafts into FVB recipients, after 6 days transgenic islets retain 60% of their original insulin content while control islets only retain less than 20% ot their initial insulin
• transgenic islets produce a lower level of reactive oxygen species after 7 hours of hypoxia than conrol islet cells

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:100251


Mouse Genome Informatics
tg2
    Tg(INS-MT2A,Tyr)1Pne/0
NOD.FVB-Tg(INS-MT2A,Tyr)1Pne
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• treatment of transgenic NOD mice with cyclophosphamide (CYP) accelerated NOD diabetes; 20 days after injection of CYP 93% of transgenic mice are diabetic compared with 7% of treated controls
• transgenic mice on the FVB background do not develop diabetes with the same regimen of CYP treatment as the NOD transgenic mice
• transgenic mice exhibit greater resistance to induced diabetes after treatment with streptozotocin compared with NOD controls

endocrine/exocrine glands
• 8 days after CYP treatment significantly more islets of transgenic NOD mice appear small and disrupted compared to treated NOD controls; percentages of damaged areas (Caspase-3 positive) in islets are 11.7 and 5.5% in transgenic NOD and control NOD mice respectively
• cultured islets of transgenic NOD mice are more sensitive to a mix of cytokines (Il-beta, Tnfa and Ifng) than NOD control islets as revealed by Caspase-3 activity
• beta cell damage is significantly increased in transgenic mice after CYP injection compared to controls; pancreatic insulin content is only 36% of original level after 8 days compared to 76% in control NOD mice

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:108415