Analysis Tools
mortality/aging
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• all homozygotes die before E6.5
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Allele Symbol Allele Name Allele ID |
Letm1Gt(DD0926)Wtsi gene trap DD0926, Wellcome Trust Sanger Institute MGI:3871268 |
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| Summary |
2 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• all homozygotes die before E6.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Small size and decreased cell proliferation in Letm1Gt(DD0926)Wtsi/Letm1+ and Letm1Gt(CC0204)Wtsi/Letm1+ mouse embryos
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• ~50% of heterozygous embryos die before E13.5
• heterozygous intercrosses yield 52.7% of heterozygotes at birth
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• E9.5 heterozygous embryos are growth-retarded
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• at E9.5
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• decreased rate of DNA synthesis (BrdU incorporation) in E9.5 heterozygous embryos
• however, no significant increase in apoptosis at E9.5, as shown by TUNEL staining
• surviving E13.5 heterozygotes appear grossly normal
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• E9.5 heterozygous embryos are growth-retarded
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• at E9.5
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• reduced mitochondrial Ca2+ (Ca2+ mito) uptake rates, low steady-state [Ca2+]mito, and decreased matrix pH in cultured primary fibroblasts derived from E13.5 heterozygous embryos relative to wild-type fibroblasts
• however, mitochondrial morphology and mitochondrial membrane potential are normal in heterozygous primary fibroblasts
• EM revaled no alterations in mitochondrial morphology in heterozygous tissues e.g. left ventricle area or hippocampus CA1 region
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• both basal and maximum oxygen consumption rates are reduced in heterozygous primary fibroblasts grown in low-glucose medium relative to wild-type fibroblasts
• however, oxygen consumption rates are normal in heterozygous fibroblasts grown in high-glucose media with pyruvate supplement
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• increases in key glycolysis intermediates are observed, consistent with a reduced mitochondrial ATP generation capacity
• reduced glucose, but not fatty acid, oxidation accounts for the differential impact of tissue [ATP]
• reduced glucose oxidation preferentially affects glucose-dependent tissues e.g. neurons and developing tissues
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• altered tryptophan metabolism in heterozygous brain tissue
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• activity of pyruvate dehydrogenase, the key rate-limiting Ca2+-sensitive enzyme that controls glucose oxidation, is significantly reduced in brain tissues after 48 h of fasting
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• increased susceptibility to kainic acid-induced seizures with initial seizure scores being 1.5-fold higher than in wild-type controls at 45 min post-kainic acid injection, and total cumulative scores increasing ~25%
• brain, but not heart, [ATP] is reduced 25% after kainic acid treatment
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• a 27% reduction in brain [ATP] is observed after 48 h of fasting at 6 weeks of age, whereas liver and heart [ATP] are not significantly altered
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• significant reduction of beta-hydroxybutyrate levels in heterozygous liver samples under normal feeding conditions
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• increased susceptibility to kainic acid-induced seizures with initial seizure scores being 1.5-fold higher than in wild-type controls at 45 min post-kainic acid injection, and total cumulative scores increasing ~25%
• brain, but not heart, [ATP] is reduced 25% after kainic acid treatment
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• modestly decreased heart/body weight ratio under resting conditions at 6 weeks of age
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| N |
• born heterozygotes appear grossly normal with no obvious facial or midline developmental defects at 6 weeks of age
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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 05/07/2024 MGI 6.23 |
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