Analysis Tools
cellular
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• following treatment with tamoxifen, mouse embryonic fibroblasts exhibit a decrease in proliferation compared to wild-type
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Allele Symbol Allele Name Allele ID |
Kat8tm1Thl targeted mutation 1, Thomas Ludwig MGI:3769362 |
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| Summary |
4 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• following treatment with tamoxifen, mouse embryonic fibroblasts exhibit a decrease in proliferation compared to wild-type
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• following treatment with tamoxifen, cell survival of mouse embryonic fibroblasts following treatment with ionizing radiation is slightly decreased compared to in wild-type cells
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• following treatment with tamoxifen, mouse embryonic fibroblasts exhibit a modest decrease in proliferation compared to wild-type
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• following treatment with tamoxifen, the number of chromosome abnormalities in mouse embryonic fibroblasts is increased compared to in wild-type cells
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• following treatment with tamoxifen, the number of chromosome abnormalities in mouse embryonic fibroblasts is increased compared to in wild-type cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 N |
• females exhibit normal fertility and ovarian follicle development relative to wild-type controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• oocytes from 2-week-old females show decreased antioxidant gene expression and increased reactive oxygen species (ROS) levels
• following daily i.p. injection of antioxidant N-acetylcysteine (NAC) for 7 days, NAC-treated oocytes show a 67.1% reduction in ROS levels relative to PBS-treated oocytes
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• TUNEL assays revealed significant oocyte apoptosis at 3 weeks of age (~17.2% versus ~5.7% in wild-type oocytes)
• following daily i.p. injection of antioxidant N-acetylcysteine (NAC) for 7 days, NAC-treated oocytes show a 56.1% reduction in TUNEL+ cells
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• ovaries contain 2-fold more atretic follicles at 3 weeks of age
• NAC-treated ovaries show a 54.7% reduction in the number of atretic follicles relative to PBS-treated ovaries
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• ovaries contain 50.4%, 49.6% and 78.7% fewer secondary, preantral and antral follicles at 3 weeks of age
• ovarian follicle development arrests in the secondary and preantral follicle stage; however, granulosa cell proliferation is normal in secondary and preantral follicles at 2 weeks of age
• TUNEL assays and gamma-H2AX immunostaining confirmed that oocytes undergoing apoptosis or exhibiting severe DNA damage are localized in secondary and preantral follicles, but not in primordial or primary follicles
• NAC-treated ovaries show a 60.0%, 83.8% and 224.2% increase in the number of secondary, preantral and antral follicles, respectively, indicating partial rescue of follicular development and survival
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• ovaries are markedly smaller at 8 weeks of age
• following daily i.p. injection of antioxidant N-acetylcysteine (NAC) for 7 days, 3-week-old NAC-treated mice have larger ovaries than PBS-treated mice; however, NAC treatment does not fully restore ovaries to wild-type size
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• females show a 77.4% reduction in ovary weight to body weight ratio at 8 weeks of age
• 3-week-old NAC-treated mice show a higher ovary weight to body weight ratio than PBS-treated mice
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• pregnant mare serum gonadotropin (PMSG)-primed females show abnormal oogenesis at 8 weeks of age
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• after PMSG priming, germinal vesicle (GV) stage oocytes are much smaller (mean diameter 63.7 um versus 81.4 um in wild-types oocytes) and show abnormal morphology, including cytoplasmic granulation, shrinkage and an irregular shape
• at 3 weeks of age, the ratio of oocytes with >5 gamma-H2AX foci is ~56.8% versus ~14.6% in wild-type oocytes, indicating severe DNA damage (double-strand breaks)
• oocytes from 2-week-old females show abnormal heterochromatin configurations: >55% of heterochromatin regions are abnormally shaped, unlike in wild-type oocytes where >80% of heterochromatin regions display a normal oval or round shape
• NAC-treated oocytes show a 58.7% reduction in double-strand breaks relative to PBS-treated oocytes
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• after PMSG priming, only ~20 full-grown germinal vesicle (GV) stage oocytes are recovered per female versus ~50 oocytes per wild-type control
• following superovulation with PMSG and HCG, more metaphase II (MII) oocytes are recovered from NAC-treated mice than from PBS-treated mice at 3 weeks of age
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• 8- to 10-week-old females fail to produce offspring during a 6-month mating period with wild-type males
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• after PMSG priming, germinal vesicle (GV) stage oocytes are much smaller (mean diameter 63.7 um versus 81.4 um in wild-types oocytes) and show abnormal morphology, including cytoplasmic granulation, shrinkage and an irregular shape
• at 3 weeks of age, the ratio of oocytes with >5 gamma-H2AX foci is ~56.8% versus ~14.6% in wild-type oocytes, indicating severe DNA damage (double-strand breaks)
• oocytes from 2-week-old females show abnormal heterochromatin configurations: >55% of heterochromatin regions are abnormally shaped, unlike in wild-type oocytes where >80% of heterochromatin regions display a normal oval or round shape
• NAC-treated oocytes show a 58.7% reduction in double-strand breaks relative to PBS-treated oocytes
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• after PMSG priming, only ~20 full-grown germinal vesicle (GV) stage oocytes are recovered per female versus ~50 oocytes per wild-type control
• following superovulation with PMSG and HCG, more metaphase II (MII) oocytes are recovered from NAC-treated mice than from PBS-treated mice at 3 weeks of age
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• 2-week-old females exhibit decreased H4K16 acetylation levels in oocytes
• however, acetylation at other detected histone residues is normal in oocytes
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• oocytes from 2-week-old females show decreased antioxidant gene expression and increased reactive oxygen species (ROS) levels
• following daily i.p. injection of antioxidant N-acetylcysteine (NAC) for 7 days, NAC-treated oocytes show a 67.1% reduction in ROS levels relative to PBS-treated oocytes
|
|
|
• TUNEL assays revealed significant oocyte apoptosis at 3 weeks of age (~17.2% versus ~5.7% in wild-type oocytes)
• following daily i.p. injection of antioxidant N-acetylcysteine (NAC) for 7 days, NAC-treated oocytes show a 56.1% reduction in TUNEL+ cells
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• oocytes from 2-week-old females show significant downregulation of antioxidant genes (e.g. Prdx1, Prdx2, Gpx1, Gpx4) and a >2-fold increase in ROS levels relative to wild-type oocytes
• NAC-treated oocytes show a 67.1% reduction in ROS levels relative to PBS-treated oocytes
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• ovaries contain 2-fold more atretic follicles at 3 weeks of age
• NAC-treated ovaries show a 54.7% reduction in the number of atretic follicles relative to PBS-treated ovaries
|
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• ovaries contain 50.4%, 49.6% and 78.7% fewer secondary, preantral and antral follicles at 3 weeks of age
• ovarian follicle development arrests in the secondary and preantral follicle stage; however, granulosa cell proliferation is normal in secondary and preantral follicles at 2 weeks of age
• TUNEL assays and gamma-H2AX immunostaining confirmed that oocytes undergoing apoptosis or exhibiting severe DNA damage are localized in secondary and preantral follicles, but not in primordial or primary follicles
• NAC-treated ovaries show a 60.0%, 83.8% and 224.2% increase in the number of secondary, preantral and antral follicles, respectively, indicating partial rescue of follicular development and survival
|
|
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• ovaries are markedly smaller at 8 weeks of age
• following daily i.p. injection of antioxidant N-acetylcysteine (NAC) for 7 days, 3-week-old NAC-treated mice have larger ovaries than PBS-treated mice; however, NAC treatment does not fully restore ovaries to wild-type size
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• females show a 77.4% reduction in ovary weight to body weight ratio at 8 weeks of age
• 3-week-old NAC-treated mice show a higher ovary weight to body weight ratio than PBS-treated mice
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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 04/16/2024 MGI 6.23 |
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