All Phenotypes Fen1<tm2.1Bhsh> MGI Mouse

• 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

increased thymus tumor incidence ( J:218627 )

• 1 of 51 (2%) homozygotes developed a thymus tumor

increased liver tumor incidence ( J:218627 )

• 4 of 51 (7.8%) homozygotes developed liver tumors

increased lung tumor incidence ( J:218627 )

• 29 of 51 (56.9%) homozygotes developed lung tumors

aneuploidy ( J:218627 )

• average % of near-tetraploid aneuploidy in mutant MEFs cells is 14.5% relative to 6.6% in wild-type MEFs

abnormal telomere morphology ( J:218627 )

• 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

abnormal cell physiology ( J:218627 )

• 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

decreased fibroblast proliferation ( J:218627 )

• 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

abnormal double-strand DNA break repair ( J:218627 )

• 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

chromosomal instability ( J:218627 )

spontaneous chromosome breakage ( J:218627 )

• mutant MEFs exhibit significantly more spontaneous chromosome breaks (2.0%) than wild-type MEFs (0.6%)