vision/eye
• lens opacities are present at 6 to 8 weeks of age and progress in severity with age
• at 1 year of age, the cataract region includes the Y-sutures forming a 'fishbone' pattern
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• punctate anterior cortical cataracts are first visible at 6 months of age
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• punctate cataracts are observed in the posterior portion of the cortex at 6 to 8 weeks of age and become obvious by 4 months of age
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• the entire lens is opaque by 18 months of age
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small lens
(
J:142278
)
• at 18 months of age, lens weight is 34% less than in wild-type mice and axial diameter is 5% smaller than in wild-type mice
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• at 18 months of age, the eye ball is smaller than in wild-type mice
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reproductive system
• TUNEL and Annexin V assays showed a significant increase in granulosa cell apoptosis
• mRNA levels of Bcl2 (an anti-apoptotic gene) are significantly decreased in granulosa cells
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• mRNA levels of cell cycle-related genes Cdk4 and Ccnd2 are significantly decreased, whereas mRNA levels of Cdkn1b (cyclin-dependent kinase inhibitor 1B, aka p27) are significantly increased in granulosa cells
• upregulation of Cdkn1b in the granulosa cells suggests a cell cycle arrest at the G1/G0 phase
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• at 11 weeks of age, the number of preovulatory follicles (with a rim of cumulus cells surrounding the oocyte) is significantly lower than that in wild-type ovaries
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• at 11 weeks of age, the number of primordial follicles is significantly lower than that in wild-type ovaries
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• at 11 weeks of age, the number of secondary follicles is significantly lower than that in wild-type ovaries
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• the number of atretic follicles per total number of follicles is significantly higher than that in wild-type ovaries
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• decreased granulosa cell proliferation delays ovarian follicular development, leading to a reduced number of primordial, secondary and preovulatory follicles
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• after induction of superovulation with PMSG + hCG treatment, the number of eggs collected from the ampulla of the oviduct is significantly lower than that in wild-type females
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• when 11-week-old female mice are mated with fertile wild-type males for 5 months, the number of pups per litter and number of litters per female is significantly reduced
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• female mice produce a significantly lower number of pups per litter than wild-type females
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cellular
• in granulosa cells, the percentage of G0/G1 phase is significantly increased, while the percentages of S and G2/M phases are significantly decreased relative to wild-type granulosa cells
• mRNA levels of cell cycle-related genes Cdk4 and Ccnd2 are significantly decreased, whereas mRNA levels of Cdkn1b (cyclin-dependent kinase inhibitor 1B, aka p27) are significantly increased in granulosa cells
• upregulation of Cdkn1b in the granulosa cells suggests a cell cycle arrest at the G1/G0 phase
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• percentage of G2/M phase is significantly decreased in granulosa cells
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• lenses exposed to hydrogen peroxide exhibit a more severe degree of opacity than similarly treated wild-type lenses
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• TUNEL and Annexin V assays showed a significant increase in granulosa cell apoptosis
• mRNA levels of Bcl2 (an anti-apoptotic gene) are significantly decreased in granulosa cells
|
• mRNA levels of cell cycle-related genes Cdk4 and Ccnd2 are significantly decreased, whereas mRNA levels of Cdkn1b (cyclin-dependent kinase inhibitor 1B, aka p27) are significantly increased in granulosa cells
• upregulation of Cdkn1b in the granulosa cells suggests a cell cycle arrest at the G1/G0 phase
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homeostasis/metabolism
• however, serum estradiol levels are normal at proestrous and estrus
• at 11 weeks of age, serum estradiol levels are significantly increased at metestrus and diestrus
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• at 11 weeks of age, serum progesterone levels are significantly decreased at diestrus
• however, serum progesterone levels are normal at other estrous cycle stages
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endocrine/exocrine glands
• TUNEL and Annexin V assays showed a significant increase in granulosa cell apoptosis
• mRNA levels of Bcl2 (an anti-apoptotic gene) are significantly decreased in granulosa cells
|
• mRNA levels of cell cycle-related genes Cdk4 and Ccnd2 are significantly decreased, whereas mRNA levels of Cdkn1b (cyclin-dependent kinase inhibitor 1B, aka p27) are significantly increased in granulosa cells
• upregulation of Cdkn1b in the granulosa cells suggests a cell cycle arrest at the G1/G0 phase
|
• at 11 weeks of age, the number of preovulatory follicles (with a rim of cumulus cells surrounding the oocyte) is significantly lower than that in wild-type ovaries
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• at 11 weeks of age, the number of primordial follicles is significantly lower than that in wild-type ovaries
|
• at 11 weeks of age, the number of secondary follicles is significantly lower than that in wild-type ovaries
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• the number of atretic follicles per total number of follicles is significantly higher than that in wild-type ovaries
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• decreased granulosa cell proliferation delays ovarian follicular development, leading to a reduced number of primordial, secondary and preovulatory follicles
|