Analysis Tools
mortality/aging
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• 3/6 males showing weight loss with severe hyperglycemia die by 41-49 weeks of age
• mice with juvenile-onset hyperglycemia did not require insulin therapy to survive to >39 weeks, whereas wild-type NOD littermates developed adult onset hyperglycemia, rapidly lost weight, and were euthanized
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growth/size/body
weight loss
(
J:118305
)
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• 35.3% (6/17) homozygous males show a persistent decrease in weight beginning at 7-9 weeks and continuing to 39 weeks of age
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• within 1 week of weaning, mice gain 6-10 grams more than wild-type littermates
• females show rapid weight gain up ~15 weeks of age to a ~stable weight of 40 grams
• males also show marked weight gain after weaning; in 64.7% of males (11/17), postpubertal (from 7 weeks of age) weight gain continues
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homeostasis/metabolism
| N |
• plasmacorticosterone levels in mutants and NOD controls are similar
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• hyperglycemia in all females and subset of males remits to normoglycemia with increasing age, while lean littermates show progression to type I diabetes
• 4/11 males showing maintained elevated body weight become normoglycemic (glucose 145 mg/dl at 39 weeks); remaining 7 males in this group are still hyperglycemic but exhibit lower mean blood glucose level (386 mg/dl) at 39 weeks
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• develops in most obese mice withing 2 weeks of weaning
• the males (6/17) showing decrease in body weight display severe hyperglycemia (glucose 581 mg/dl at 39 weeks)
• by 5-7 weeks of age, 4/5 females and 11/17 males are hyperglycemic (glucose >200 mg/dl) and most remain hyperglycemic through the peripubertal period (253-686 mg/dl at 13 weeks)
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• levels increase markedly above lean controls with age
• females remitting to normoglycemia still exhibit elevated insulin levels; males showing weight loss display reduced insulin levels (~nondiabetic control), while males maintaining elevated weight still show elevated levels
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• levels increase markedly above lean controls with age
• females remitting to normoglycemia still exhibit elevated leptin levels
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endocrine/exocrine glands
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• animals that maintained high body weight with or without remission from intermediate levels of hyperglycemia have extremely hyperplastic islets with well-granulated beta cells; islets display peri-insulitis
• males exhibiting unrestrained hyperglycemia and weight loss have islets reduced in size and number of granulated beta cells, but showing minimal intraislet insulitis
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• islets are normal-sized with markedly degranulated beta cells
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• perivascular/periductular infiltrates are present but nor intraislet infiltrates are observed
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behavior/neurological
polyphagia
(
J:118305
)
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• early weight gain is associated with hyperphagia; at 5 weeks, mice consume twice as much as lean controls
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adipose tissue
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• at 15 weeks, females have 40.5% carcass fat vs 19.9% in lean littermates; males show 33% body fat vs 14.7% in lean males
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immune system
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• perivascular/periductular infiltrates are present but nor intraislet infiltrates are observed
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• CD4+ CD25+ T cells are slightly reduced in percentage compared to control NOD/LtJ mice (8.0 vs 9.5%)
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• beta cell autoreactive CD8+ T cell clonotypes are decreased in mutants compared to NOD controls; IGRP and insulin-reactive CD8+ clonotypes are 5.7- and 1.7-fold lower in spleens of female mutants compared to controls
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hematopoietic system
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• CD4+ CD25+ T cells are slightly reduced in percentage compared to control NOD/LtJ mice (8.0 vs 9.5%)
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• beta cell autoreactive CD8+ T cell clonotypes are decreased in mutants compared to NOD controls; IGRP and insulin-reactive CD8+ clonotypes are 5.7- and 1.7-fold lower in spleens of female mutants compared to controls
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