Phenotypes associated with this allele

• Allele Symbol: Ino80^tm1Schg
• Allele Name: targeted mutation 1, Sandy Chang
• Allele ID: MGI:5698824
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ino80^tm1Schg/Ino80^tm1Schg Tg(CAG-cre/Esr1*)5Amc/0	involves: C57BL/6 * CBA	MGI:5898009

Genotype
MGI:5898009

cn1

• Allelic Composition: Ino80^tm1Schg/Ino80^tm1Schg; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: C57BL/6 * CBA

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:221224 )

• 50% of mice die by 170 days after 3 tamoxifen injections at 6-8 weeks of age

cellular

cellular phenotype ( J:221224 )

N • all phenotypes detected after cre induction in MEFs

abnormal telomere morphology ( J:221224 )

• a 1.7-fold increase in multiple telomeric signals (MTS, fragile telomeres); however, telomere length is not affected

abnormal cell physiology ( J:221224 )

• 4-hydroxytamoxifen (4-HT) treated MEFs are hypersensitive to hydroxyurea and aphidicolin, showing decreased colony forming after exposure

abnormal cell cycle ( J:221224 )

• defect in S-phase progression

increased cellular sensitivity to alkylating agents ( J:221224 )

• decreased survival of following exposure to hydroxyurea or aphicicolin

increased cellular sensitivity to hydroxyurea ( J:221224 )

increased cellular sensitivity to ultraviolet irradiation ( J:221224 )

• decreased survival 48h after UV exposure

decreased fibroblast proliferation ( J:221224 )

• cells stopped proliferation 4 days after cre induction

early cellular replicative senescence ( J:221224 )

• a higher percentage of 4-HT treated MEFs show increased staining at early passages for the senescence marker SA-beta-galactosidase which correlates with induction of p21 expression suggesting premature entry into cellular senescence/cell cycle arrest

abnormal DNA repair ( J:221224 )

• MEFs exposed to UV following 4-HT treatment exhibit a reduction in the efficiency of UV repair by the nucleotide excision repair pathway, showing delayed removal of UV-induced photo lesions and decreased cellular survival 48 hours after UV exposure

abnormal double-strand DNA break repair ( J:221224 )

• reduced efficiency of repair of ionizing radiation-induced double-stranded breaks, UV-induced photo lesions and dysfunctional telomeres

abnormal DNA replication ( J:221224 )

• 4-HT treated MEFs exhibit defects in ssDNA formation and telomere replication

• 4-HT treated MEFs exhibit a 1.7-fold increase in the number of multiple telomere signals, indicating defects in telomere replication

growth/size/body

decreased body weight ( J:221224 )

• mice injected with tamoxifen at 6-8 weeks of age exhibit reduced body weight

homeostasis/metabolism

abnormal DNA repair ( J:221224 )

• MEFs exposed to UV following 4-HT treatment exhibit a reduction in the efficiency of UV repair by the nucleotide excision repair pathway, showing delayed removal of UV-induced photo lesions and decreased cellular survival 48 hours after UV exposure

abnormal double-strand DNA break repair ( J:221224 )

• reduced efficiency of repair of ionizing radiation-induced double-stranded breaks, UV-induced photo lesions and dysfunctional telomeres

abnormal DNA replication ( J:221224 )

• 4-HT treated MEFs exhibit defects in ssDNA formation and telomere replication

• 4-HT treated MEFs exhibit a 1.7-fold increase in the number of multiple telomere signals, indicating defects in telomere replication

abnormal response to radiation ( J:221224 )

• reduced efficiency of repair of ionizing radiation-induced double-stranded breaks

neoplasm

neoplasm ( J:221224 )

N • tamoxifen treated mice do not exhibit increased tumor incidence