Analysis Tools
immune system
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• present in pancreata of some but not all non-diabetic hemizygotes at 30 weeks of age; 2/22 males and 3/17 females showed widespread invasive insulitis, while in 13/22 males and 9/17 females, no intra-islet insulitis was observed along with hyperplastic/hypertrophic increases in islet size; remaining males and females showed combination of insulitic and insulitis-free islets
• in a subset of non-diabetic animals at 30 weeks, some mice show widespread invasive insulitis
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• development of clinical diabetes is almost completely suppressed in hemizygous females followed to 30 weeks of age, whereas hemizygous males develop a low frequency of clinical diabetes (30-40%) that was comparable to NOD/ShiLtJ control males
• cyclophosphamide-injected 8 week old females all developed diabetes within 12 days, but only 2/6 injected transgenic females (at 22 weeks of age) develop disease
• when diabetogenic CD8+ T-effector cells from NOD.Cg-Rag1tm1Mom Tg(TcraAI4)1Dvs Tg(TcrbAI4)1Dvs or NOD.Cg-Tg(TcraTcrbNY8.3)1Pesa mice are adoptively transferred to irradiated female NOD/ShiLtJ-Tg(Ins1-EGFP/GH1)14Hara mice and control NOD/ShiLt mice, ~25% of transgenic recipients become diabetic by 11 days post-transfer compared to 5/8 control females
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endocrine/exocrine glands
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• many islets of insulitis-free animals and animals displaying a mix of insulitic and normal islets show peri-insular and intra-islet fibrosis, in contrast to NOD/ShiLt controls
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• present in pancreata of some but not all non-diabetic hemizygotes at 30 weeks of age; 2/22 males and 3/17 females showed widespread invasive insulitis, while in 13/22 males and 9/17 females, no intra-islet insulitis was observed along with hyperplastic/hypertrophic increases in islet size; remaining males and females showed combination of insulitic and insulitis-free islets
• in a subset of non-diabetic animals at 30 weeks, some mice show widespread invasive insulitis
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homeostasis/metabolism
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• in 30-week old hemizygous males, there is a 2-fold decrease in plasma insulin content compared to non-diabetic NOD/ShiLt controls
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• impaired glucose tolerance is observed at 8 weeks in hemizygotes in comparison to NOD/ShiLt controls; at 28 weeks, impairment is significantly greater than at 8 weeks
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