Analysis Tools
normal phenotype
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• at 8 weeks of age, mice exhibit normal glucose tolerance and body weight relative to wild-type controls
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Allele Symbol Allele Name Allele ID |
Clec16atm1.1Hhak targeted mutation 1.1, Hakon Hakonarson MGI:5648633 |
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| Summary |
3 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at 8 weeks of age, mice exhibit normal glucose tolerance and body weight relative to wild-type controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• OHT-treated fibroblasts show a defect in trafficking of autophagosomes to the lysosomal compartment during late mitophagy
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• hydroxytamoxifen (OHT)-treated primary dermal fibroblasts exhibit a reduced oxygen consumption rate relative to controls
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• OHT-treated fibroblasts show a defect in trafficking of autophagosomes to the lysosomal compartment during late mitophagy
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• accumulation of unhealthy mitochondria, coupled with dysregulation of the Nrdp1/Parkin pathway, suggests defective mitophagy/autophagy leading to impaired glucose-stimulated OCR and insulin secretion
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• mice show reduced basal and blunted insulin release at 0 and 3 min after glucose administration in vivo and in isolated islets
• no differences in peripheral insulin sensitivity are observed
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• mice exhibit hyperglycemia due to functional defects in beta cells
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• pancreatic islets show reduced glucose-stimulated oxygen consumption rate (OCR) as well as maximal OCR following FCCP treatment (to induce mitophagy) relative to wild-type islets
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• intraperitoneal glucose tolerance testing (IPGTT) revealed that mice are significantly hyperglycemic relative to controls
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| N |
• no signs of exocrine pancreatic dysfunction, such as weight loss, steatorrhea, or abnormal acinar or ductal cell histology
• no evidence of infiltrating lymphocytes into the pancreatic islets
• normal islet architecture and beta cell mass
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• pancreatic alpha cells exhibit rounded mitochondria with a severely disordered and amorphous structure
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• at 3 months, TEM revealed an accumulation of vacuolated structures, some containing partially degraded cytoplasmic material consistent with autophagic vacuoles, not observed in wild-type beta cells
• beta cells exhibit rounded mitochondria with a severely disordered and amorphous structure, including an increased number of distorted cristae and inclusions not observed in wild-type cells
• 3D EM reconstruction tomography showed accumulation of electron lucent vacuolated structures, including large interconnected vacuoles (likely dilated ER), and smaller spherical vacuoles (possibly endosomes)
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• mice show a significant increase in total pancreatic insulin content at age 12 weeks
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• mice show reduced basal and blunted insulin release at 0 and 3 min after glucose administration in vivo and in isolated islets
• no differences in peripheral insulin sensitivity are observed
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• pancreatic beta cells show age-dependent alterations in ER morphology, indicative of ER stress
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• pancreatic beta cells exhibit rounded mitochondria with a severely disordered and amorphous structure, including an increased number of distorted cristae and inclusions not observed in wild-type cells
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• distorted mitochondrial cristae in pancreatic beta cells
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• increased mitochondrial mass in pancreatic islets, as shown by increased mtDNA levels and levels of the mitochondrial proteins succinate dehydrogenase A and mitochondrial complex IV subunit I
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• accumulation of unhealthy mitochondria, coupled with dysregulation of the Nrdp1/Parkin pathway, suggests defective mitophagy/autophagy leading to impaired glucose-stimulated OCR and insulin secretion
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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 08/02/2024 MGI 6.24 |
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