Analysis Tools|
Allele Symbol Allele Name Allele ID |
Ins1tm1.1(cre)Thor targeted mutation 1.1, Bernard Thorens MGI:5614359 |
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| Summary |
7 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal body weight
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| N |
• mice exhibit normal random fed glycemia levels and glucose tolerance
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• locus is maternally imprinted with no gene expression detectable in mice that have paternally inherited the mutant allele
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• mice inheriting the allele paternally exhibit impaired glucose-stimulated insulin secretion
• mice with the paternally inherited allele do not show a normal hyperinsulinemic response to Western diet exposure, with persistence of the defect in glucose-stimulated insulin secretion seen on chow diet
• pancreatic beta cells from mice with the paternally inherited allele show a 2-fold increase in insulin secretion with high glucose compared to 7.2-fold increase by wild-type cells
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• mice inheriting the allele paternally exhibit impaired glucose-stimulated insulin secretion
• mice with the paternally inherited allele do not show a normal hyperinsulinemic response to Western diet exposure, with persistence of the defect in glucose-stimulated insulin secretion seen on chow diet
• pancreatic beta cells from mice with the paternally inherited allele show a 2-fold increase in insulin secretion with high glucose compared to 7.2-fold increase by wild-type cells
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• fasting blood glucose progressively increases in mice that inherit the paternal allele during exposure to Western diet
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• progressive deterioration of glucose tolerance is seen over 12 weeks in males with the paternal allele on the Western diet
• however, glucose tolerance is unaffected in chow-fed mice with the paternal allele
• however, no differences in body weight or insulin sensitivity are seen on the Western diet in mice with the paternally inherited allele, suggesting a decline in beta cell function
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• when fed a high fat diet, mice show no differences in beta cell mass or in glucose tolerance and insulin secretion following intraperitoneal glucose injections relative to similarly treated control mice
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• primary pancreatic islet cells exhibit reduced sensitivity to cytokines- or palmitic acid-induced apoptosis, as measured by a TUNEL assay
• islets show increased expression of the anti-apoptotic proteins Bcl2, Bcl2l1 (Bcl-xL), as well as increased expression and phosphorylation of Bad, which inhibits its pro-apoptotic activity
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• primary pancreatic islet cells exhibit reduced sensitivity to cytokines- or palmitic acid-induced apoptosis, as measured by a TUNEL assay
• islets show increased expression of the anti-apoptotic proteins Bcl2, Bcl2l1 (Bcl-xL), as well as increased expression and phosphorylation of Bad, which inhibits its pro-apoptotic activity
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice show normal endocrine cell egression and normal numbers of pancreatic alpha and beta cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are overtly normal and exhibit normal growth rates and intraperitoneal and oral glucose tolerance with no differences in glucose-induced Ca2+ dynamics or insulin secretion in isolated islets relative to control mice
• mutant islets show normal glucagon-like peptide-1 (GLP-1)-induced Ca2+ dynamics and insulin secretion, with a similar increase in GLP-1-induced Ca2+ oscillation frequency during moderate glucose stimulation relative to control islets
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• despite an 80% reduction in Larp1 expression by islets, male mice exhibit no difference in glucose tolerance relative to control males
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• at 8 weeks of age, pancreata show normal gross islet morphology with no change in the number of insulin-positive beta cells, glucagon-positive alpha cells, or total pancreatic cells relative to controls
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• RNA-seq on islets of 8-week-old mice shows downregulation of beta-cell maturation markers, including Ucn3 (urocortin 3), Mafa (MAF bZIP transcription factor A), Slc2a2/Glut2 [solute carrier family 2 (facilitated glucose transporter, member 2], Slc30a8 [solute carrier family 30 (zinc transporter), member 8], Iapp (islet amyloid polypeptide), and Ero1b (endoplasmic reticulum oxidoreductase 1 beta)
• islets of 8-week-old mice show significantly fewer and smaller dense core insulin granules, indicating impaired mature insulin secretory granule formation and beta-cell maturation
• at P1 to 8 weeks of age, islets show complete loss of Mafa, Ucn3, and Slc2a2/Glut2 immunostaining (markers of glucose-responsive beta-cells)
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• pancreatic islets show reduced glucose-stimulated oxygen consumption but no change in maximal respiration (after addition of FCCP)
• islets show significantly reduced mitochondrial membrane potential upon stimulation with glucose, but not following stimulation with the mitochondrial substrate alpha-ketoglutarate
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• at 3 weeks of age, pancreatic beta cell proliferation is significantly increased, as assessed by EdU incorporation into nuclei
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• in perifusion assays, pancreatic islets of 8-week-old mice stimulated with 25 mM glucose show impaired first- and second-phase insulin secretion, with no significant change in total insulin content
• however, islets stimulated with alpha-ketoglutarate or KCl show normal insulin secretion, suggesting a defect upstream of mitochondrial metabolism
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• in perifusion assays, pancreatic islets of 8-week-old mice stimulated with 25 mM glucose show impaired first- and second-phase insulin secretion, with no significant change in total insulin content
• however, islets stimulated with alpha-ketoglutarate or KCl show normal insulin secretion, suggesting a defect upstream of mitochondrial metabolism
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• at 3 and 8 weeks of age, both male and female mice show significantly decreased serum insulin levels at time 0 (fasting) and 10 min after intraperitoneal glucose injection
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• at 3, 6, and 8 weeks of age, intraperitoneal glucose tolerance tests show that both male and female mice are severely glucose intolerant
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• pancreatic islets show a significant reduction in mitochondrial count per cell relative to control islets
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• pancreatic islets show a significant increase in average mitochondrial volume relative to control islets
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• islets of 8-week-old mice show significantly fewer and smaller dense core insulin granules, indicating impaired mature insulin secretory granule formation and beta-cell maturation
• at P1 to 8 weeks of age, islets show complete loss of Mafa, Ucn3, and Slc2a2/Glut2 immunostaining (markers of glucose-responsive beta-cells)
• RNA-seq on islets of 8-week-old mice shows downregulation of beta-cell maturation markers, including Ucn3 (urocortin 3), Mafa (MAF bZIP transcription factor A), Slc2a2/Glut2 [solute carrier family 2 (facilitated glucose transporter, member 2], Slc30a8 [solute carrier family 30 (zinc transporter), member 8], Iapp (islet amyloid polypeptide), and Ero1b (endoplasmic reticulum oxidoreductase 1 beta)
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• at 3 weeks of age, pancreatic beta cell proliferation is significantly increased, as assessed by EdU incorporation into nuclei
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• dispersed pancreatic islets from 8-week-old mice show significantly reduced glucose uptake, as measured by 2-NBDG (a glucose analog), relative to control islets
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• pancreatic islets appear to show altered mitochondrial fission/fusion dynamics, likely due to beta cell immaturity
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| N |
• 8-week-old mice (male and female combined) exhibit normal body weight relative to age-matched controls
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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 03/25/2025 MGI 6.24 |
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