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Allele Symbol Allele Name Allele ID |
Ins1tm1.1(cre)Thor targeted mutation 1.1, Bernard Thorens MGI:5614359 |
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| Summary |
5 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 |
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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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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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