|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean beta cell mass slightly but significantly more than in wild-type controls
|
|
• limited hyperplasia
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Severe insulitis in Ins2tm1Jja/Ins2tm1Jja mice and lack of insulitis in Ins1tm1Jja/Ins1tm1Jja mice
|
• homozygotes are resistant to diabetes and insulitis development on the NOD background; whereas 13 of 15 wild-type NOD mice develop insulitis, only 1 of 19 homozygotes develop diabetes
• homozygous islets transplanted under the kidney capsule of recent onset NOD wild-type mice reversed the hyperglycemia and maintained euglycemia for a week or longer
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| NOT | type 1 diabetes mellitus | DOID:9744 |
OMIM:222100 |
J:85309 |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• by 4 weeks after birth, few insulin positive beta-cells are present in pancreata
|
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• function is impaired as indicated by lower circulating insulin levels
|
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• islets in pancreata of diabetic mice contain CD8+ and CD4+ T cells, B-cells, and macrophages at 3 weeks
|
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• after postnatal day 10, mice begin to develop elevated blood sugar level compare to controls
|
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• by 3 weeks of age, both males and females exhibit severe hyperglycemia
|
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• levels are significantly lower at 3 weeks compared to controls
|
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• mice show impaired immune tolerance towards insulin; tolerance towards other autoantigens is unimpaired
|
|
• islets in pancreata of diabetic mice contain CD8+ and CD4+ T cells, B-cells, and macrophages at 3 weeks
|
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• upon stimulation with insulin, interferon-gamma secreting T cells are detected;
• pancreata of nude mice that received transplants of thymi from diabetic mutants display insulitis with T cell infiltrates at 16 weeks after transplantation
• Rag1 mice that received transfer of splenocytes from diabetic mutants show elevated blood glucose at 1-2 weeks after transfer with autoreactive T cells detected; at 4 weeks after transfer of CD4+ or CD8+ T cells, pancreata of Rag1 mice show insulitis and beta-cell destruction
|
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• insulin-stimulated T cells show high production of interferon-gamma
|
|
• levels of anti-insulin autoantibodies in sera of 3-8 week old mice are significantly higher than in controls
|
|
• upon stimulation with insulin, interferon-gamma secreting T cells are detected;
• pancreata of nude mice that received transplants of thymi from diabetic mutants display insulitis with T cell infiltrates at 16 weeks after transplantation
• Rag1 mice that received transfer of splenocytes from diabetic mutants show elevated blood glucose at 1-2 weeks after transfer with autoreactive T cells detected; at 4 weeks after transfer of CD4+ or CD8+ T cells, pancreata of Rag1 mice show insulitis and beta-cell destruction
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Growth retardation of Ins1tm1Jja/Ins1tm1Jja Ins2tm1Jja/Ins2tm1Jja mice
|
• death in 48 hours after birth on average
|
|
• significant hyperplasia
|
|
• about 1.5X larger than in littermate controls
|
|
• milky plasma
|
|
• severely diabetic
(J:77595)
|
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• glycosuria detectable after pups suckle
|
|
• mean body weight within a few hours of birth 22% less than littermate controls
|
|
• glycosuria detectable after pups suckle
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| maturity-onset diabetes of the young | DOID:0050524 |
OMIM:606391 |
J:40377 , J:77595 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• double homozygous mice die 2-3 days after birth
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at birth the relative reduction in body weight is 22%
|
|
• at E18.5, body weight is reduced by 15% compared to heterozygous pups
|
|
• there is decreased islet cell apoptosis in in all regions of the islets compared to controls
|
|
• at E18.5 there is increased islet cell proliferation compared to controls, with both alpha and beta cells proliferating
|
|
• at E18.5 there is increased islet cell proliferation compared to controls, with both alpha and beta cells proliferating
|
|
• there is decreased islet cell apoptosis in in all regions of the islets compared to controls
|
|
• at E18.5 there is increased islet cell proliferation compared to controls, with both alpha and beta cells proliferating
|
|
• at E18.5 there is increased islet cell proliferation compared to controls, with both alpha and beta cells proliferating
|
|
• total alpha cell mass is increased compared to wild-type and Ins1-null, Ins2-heterozygous controls (38 ug w.t. vs 45 ug vs 68 ug double nulls)
|
|
• total beta cell mass at E18.5, is 348 ug compared to 226 ug in Ins1-null, Ins2-heterozygous controls
|
|
• mean islet area is significantly increased compared with Ins1-null, Ins2-heterozygous controls at E18.5 and P1 but not at E17.5
• compared to wild-type controls, mice have more large islets and fewer small islets
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• total alpha cell mass is increased compared to wild-type (68 ug vs 48 ug w.t.)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• male transgenic mice lacking both native insulin genes develop diabetes before 10 weeks of age (2 consecutive measurements of >250 mg/dl glucose)
|
|
• at 26 weeks of age, sialitis is observed but not insulitis
|
|
• female transgenic mice lacking both native insulin genes do not exhibit diabetes by 30 weeks of age
|
|
• at 26 weeks of age, sialitis is observed but not insulitis
|
|
• at 26 weeks of age, sialitis is observed but not insulitis
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| NOT | type 1 diabetes mellitus | DOID:9744 |
OMIM:222100 |
J:98583 |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 26 weeks of age, sialitis is observed but not insulitis
|
|
• no female double knockout mice carrying the transgene on a NOD background develop diabetes over 30 weeks of observation
|
|
• females lacking both insulin genes do not produce insulin autoantibodies
|
|
• at 26 weeks of age, sialitis is observed but not insulitis
|
|
• at 26 weeks of age, sialitis is observed but not insulitis
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| NOT | type 1 diabetes mellitus | DOID:9744 |
OMIM:222100 |
J:98583 |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 75% of female transgenic mice lacking Ins2 develop diabetes (2 consecutive blood glucose measurements of >250 mg/dl) by 25 weeks of age
|
|
• >250 mg/dl blood glucose is considered diabetic
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| type 1 diabetes mellitus | DOID:9744 |
OMIM:222100 |
J:98583 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• female transgenic mice lacking the Ins2 gene do not show any increased resistance to diabetes compared to nontransgenic mice lacking the gene
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/23/2024 MGI 6.23 |
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