Analysis Tools
neoplasm
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• between 14 and 20 months of age, homozygotes exhibit a higher spontaneous tumor incidence than wild-type controls
• overall, 38 of 51 (74.5%) homozygotes developed various types of tumors relative to only 9 of 51 (17.6%) wild-type mice which only developed lung tumors
• 4 of 51 (7.8%) homozygotes developed spleen tumors
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• 1 of 51 (2%) homozygotes developed a thymus tumor
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• 4 of 51 (7.8%) homozygotes developed liver tumors
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• 29 of 51 (56.9%) homozygotes developed lung tumors
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cellular
aneuploidy
(
J:218627
)
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• average % of near-tetraploid aneuploidy in mutant MEFs cells is 14.5% relative to 6.6% in wild-type MEFs
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• FISH analysis revealed that spontaneous telomere fragility is 1.5-fold higher in mutant MEFs (4.3%) relative to wild-type MEFs (2.7%), with one fragile telomere occurring per 23 telomeres versus 37 telomeres in wild-type cells
• telomere fragility on the lagging strand is 2.3% in mutant MEFs relative to 1.2% in wild-type MEFs, whereas fragility on the leading strand is 0.5% in mutant and 0.15% in wild-type MEFs
• telomere loss for lagging strands is 0.85% in mutant MEFs and 0.45% in wild-type MEF), whereas telomere loss in leading strands is 0.75% in mutant and 0.3% in wild-type MEFs
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• in vitro cellular transformation assays revealed that the number of colonies formed by mutant MEFs is 9-fold higher than in wild-type MEFs, indicating a high transformation potential
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• under normal culture conditions, mutant MEFs show mild-to-moderate defects in cell growth relative to wild-type MEFs
• upon treatment with camptothecin (CPT), a chemical reagent that causes stall of DNA replication forks in cells, the number of mutant live cells is decreased by 3% per day, whereas the number of wild-type cells is increased by 10% per day
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• in response to UV and camptothecin (CPT) treatment, mutant MEFs isolated from E13 embryos accumulate significantly more double-strand DNA breaks than wild-type MEFs, as determined by gammaH2AX staining
• however, untreated wild-type and mutant MEFs show little or no positive gammaH2AX staining
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• mutant MEFs exhibit significantly more spontaneous chromosome breaks (2.0%) than wild-type MEFs (0.6%)
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homeostasis/metabolism
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• in response to UV and camptothecin (CPT) treatment, mutant MEFs isolated from E13 embryos accumulate significantly more double-strand DNA breaks than wild-type MEFs, as determined by gammaH2AX staining
• however, untreated wild-type and mutant MEFs show little or no positive gammaH2AX staining
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respiratory system
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• 29 of 51 (56.9%) homozygotes developed lung tumors
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endocrine/exocrine glands
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• 1 of 51 (2%) homozygotes developed a thymus tumor
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liver/biliary system
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• 4 of 51 (7.8%) homozygotes developed liver tumors
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hematopoietic system
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• 1 of 51 (2%) homozygotes developed a thymus tumor
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immune system
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• 1 of 51 (2%) homozygotes developed a thymus tumor
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