Phenotypes Associated with This Genotype

Genotype
MGI:6850619

• Allelic Composition: Bmi1^tm1Brn/Bmi1^tm1Brn
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * FVB/N

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

reproductive system

decreased oocyte number ( J:287217 )

♀ • number of retrieved oocytes per mouse is significantly lower than that for wild-type females

♀ • administration of antioxidant N-acetylcysteine (NAC) in the drinking water from 3 to 7 weeks of age increases the number of retrieved oocytes significantly but does not restore oocyte number to wild-type levels

decreased mature ovarian follicle number ( J:287217 )

♀ • the number of mature follicles per ovary is markedly reduced at 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age results in a marked increase in mature ovarian follicle number

decreased primary ovarian follicle number ( J:287217 )

♀ • the number of primary follicles per ovary is markedly reduced at 1, 4, and 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age has no significant effect on primary ovarian follicle number

decreased primordial ovarian follicle number ( J:287217 )

♀ • the number of primordial follicles per ovary is markedly reduced at 1, 4, and 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age has no significant effect on primordial ovarian follicle number

decreased secondary ovarian follicle number ( J:287217 )

♀ • the number of secondary follicles per ovary is markedly reduced at 4 and 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age results in a marked increase in secondary ovarian follicle number

increased atretic ovarian follicle number ( J:287217 )

♀ • the number of atretic ovarian follicles is markedly increased at 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age results in a marked decrease in atretic follicle number

abnormal ovary development ( J:287217 )

♀

small ovary ( J:287217 )

♀ • ovary size is significantly smaller at 7 weeks of age

♀ • administration of antioxidant N-acetylcysteine (NAC) in the drinking water from 3 to 7 weeks of age results in a marked increase in ovary size

decreased ovary weight ( J:287217 )

♀ • ovarian weight and ovarian weight/body weight ratio are significantly decreased at 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age results in a marked increase in ovarian weight and ovarian weight/body weight ratio

abnormal ovary physiology ( J:287217 )

♀ • protein levels of p16, p19 and p53 are markedly increased whereas anti-apoptotic BCL-2 protein levels are decreased in ovarian extracts from 7-week-old female mice

♀ • numbers of 8-OHdG+ cells and gammaH2AX+ cells are dramatically increased in ovarian sections at 7 weeks of age, indicating increased DNA damage

♀ • % of BrdU+ cells is significantly reduced at 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age results in markedly reduced numbers of 8-OHdG+ cells and gammaH2AX+ cells while % of BrdU+ cells is increased

increased granulosa cell apoptosis ( J:287217 )

♀ • % of Caspase-3+ granulosa cells is significantly increased at 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age results in markedly reduced % of Caspase-3+ cells

decreased granulosa cell proliferation ( J:287217 )

♀ • % of PCNA+ granulosa cells is significantly reduced at 7 weeks of age

delayed vaginal opening ( J:287217 )

♀ • vaginal opening time is markedly delayed

decreased superovulation rate ( J:287217 )

♀ • following induction of superovulation with PMSG and hCG, significantly fewer oocytes are retrieved from the ampulla portion of 3-week old females relative to similarly treated wild-type females

abnormal estrous cycle ( J:287217 )

♀

prolonged diestrus ( J:287217 )

♀ • % of time spent in diestrus per 5 days is significantly increased

short estrus ( J:287217 )

♀ • % of time spent in estrus per 5 days is significantly reduced

prolonged metestrus ( J:287217 )

♀ • % of time spent in metestrus per 5 days is significantly increased

short proestrus ( J:287217 )

♀ • % of time spent in proestrus per 5 days is significantly reduced

female infertility ( J:287217 )

♀ • female mice mated with adult wild-type males of known fertility for 1 month fail to produce offspring, indicating complete female sterility

cellular

decreased oocyte number ( J:287217 )

♀ • number of retrieved oocytes per mouse is significantly lower than that for wild-type females

♀ • administration of antioxidant N-acetylcysteine (NAC) in the drinking water from 3 to 7 weeks of age increases the number of retrieved oocytes significantly but does not restore oocyte number to wild-type levels

abnormal mitochondrial morphology ( J:287217 )

♀ • TEM images of granulosa cells and oocytes showed that the mitochondrial outer membrane is indistinct and defective

abnormal mitochondrial crista morphology ( J:287217 )

♀ • some mitochondrial crest blurring or even swelling is observed in the ovaries

decreased mitochondrial number ( J:287217 )

♀ • the number of mitochondria is significantly reduced in the ovaries at 7 weeks of age

increased granulosa cell apoptosis ( J:287217 )

♀ • % of Caspase-3+ granulosa cells is significantly increased at 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age results in markedly reduced % of Caspase-3+ cells

decreased granulosa cell proliferation ( J:287217 )

♀ • % of PCNA+ granulosa cells is significantly reduced at 7 weeks of age

oxidative stress ( J:287217 )

♀ • flow cytometry analysis showed increased reactive oxygen species (ROS) levels in the ovaries at 7 weeks of age

♀ • mRNA expression levels of antioxidant enzyme genes (Sod1, Sod2, Gpx1, Gsr, Cat, and Txnrd1) and the protein levels of SOD1 and SOD2 are significantly decreased in ovarian extracts from 7-week-old female mice

♀ • antioxidant NAC administration from 3 to 7 weeks of age results in markedly decreased ROS levels while protein levels of SOD1 and SOD2 are significantly increased

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:287217 )

♀ • mRNA expression levels of antioxidant enzyme genes (Sod1, Sod2, Gpx1, Gsr, Cat, and Txnrd1) and the protein levels of SOD1 and SOD2 are significantly decreased in ovarian extracts from 7-week-old female mice

decreased superoxide dismutase level ( J:287217 )

♀ • both mRNA and protein levels of Sod1 (superoxide dismutase 1) and Sod2 (superoxide dismutase 2) are significantly decreased in ovarian extracts from 7-week-old female mice

embryo

failure of zygotic cell division ( J:287217 )

♀ • in vitro, oocytes derived from mice treated with IVF fail to develop into 2-cell stage embryos

♀ • surprisingly, antioxidant NAC supplementation rescues the ability of oocytes to develop into early embryos in vitro (including 2-cells, 4-cells, and blastocysts) to nearly wild-type levels

endocrine/exocrine glands

decreased mature ovarian follicle number ( J:287217 )

♀ • the number of mature follicles per ovary is markedly reduced at 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age results in a marked increase in mature ovarian follicle number

decreased primary ovarian follicle number ( J:287217 )

♀ • the number of primary follicles per ovary is markedly reduced at 1, 4, and 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age has no significant effect on primary ovarian follicle number

decreased primordial ovarian follicle number ( J:287217 )

♀ • the number of primordial follicles per ovary is markedly reduced at 1, 4, and 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age has no significant effect on primordial ovarian follicle number

decreased secondary ovarian follicle number ( J:287217 )

♀ • the number of secondary follicles per ovary is markedly reduced at 4 and 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age results in a marked increase in secondary ovarian follicle number

increased atretic ovarian follicle number ( J:287217 )

♀ • the number of atretic ovarian follicles is markedly increased at 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age results in a marked decrease in atretic follicle number

abnormal ovary development ( J:287217 )

♀

small ovary ( J:287217 )

♀ • ovary size is significantly smaller at 7 weeks of age

♀ • administration of antioxidant N-acetylcysteine (NAC) in the drinking water from 3 to 7 weeks of age results in a marked increase in ovary size

decreased ovary weight ( J:287217 )

♀ • ovarian weight and ovarian weight/body weight ratio are significantly decreased at 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age results in a marked increase in ovarian weight and ovarian weight/body weight ratio

abnormal ovary physiology ( J:287217 )

♀ • protein levels of p16, p19 and p53 are markedly increased whereas anti-apoptotic BCL-2 protein levels are decreased in ovarian extracts from 7-week-old female mice

♀ • numbers of 8-OHdG+ cells and gammaH2AX+ cells are dramatically increased in ovarian sections at 7 weeks of age, indicating increased DNA damage

♀ • % of BrdU+ cells is significantly reduced at 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age results in markedly reduced numbers of 8-OHdG+ cells and gammaH2AX+ cells while % of BrdU+ cells is increased

increased granulosa cell apoptosis ( J:287217 )

♀ • % of Caspase-3+ granulosa cells is significantly increased at 7 weeks of age

♀ • antioxidant NAC administration from 3 to 7 weeks of age results in markedly reduced % of Caspase-3+ cells

decreased granulosa cell proliferation ( J:287217 )

♀ • % of PCNA+ granulosa cells is significantly reduced at 7 weeks of age