Analysis Tools
reproductive system
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• male mice exhibit normal fertility
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• after in vitro fertilization with wild-type sperm, neither cleavage nor blastocyst formation are observed and oocytes gradually degenerate in culture
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• consistent with a delay in anaphase I onset, ~73% of MI-oocytes stain positively for BUB1B (mitotic checkpoint serine/threonine kinase, aka BUBR1) expression at their kinetochores, indicating prolonged activation of the SAC
• however, oocytes show no alterations in the timing of meiotic progression to MI, the MI-spindle assembly and chromosome alignment, or microtubule attachment to kinetochores
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• a subset of LSM14B-bound mRNAs that are crucial for oogenesis show significantly decreased translational efficiency
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• most ovulated eggs (80%) exhibit a visible first polar body (PB1) and pronucleus (PN)
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• oocytes fail to progress to metaphase II (MII); most ovulated eggs (80%) arrest at interphase with a prominent pronucleus (PN)-like internal structure, unlike wild-type ovulated eggs that arrest at MII
• metaphase I-to-anaphase I (MI-to-AI) transition and first polar body emission (PBE) are both significantly delayed (3-5 h) and activation of the spindle assembly checkpoint (SAC) is prolonged
• chemical inhibition of the TTK (MPS1) kinase by AZ3146 treatment to pass the SAC completely rescues the prolonged MI and delayed PBE defects
• prolonged MI and failed progression to MII are likely caused by delayed activation of the anaphase-promoting complex (APC) at the end of MI and an inability to reactivate maturation-promoting factor (MPF) after MI-to-AI transition
• GV-stage fully-grown oocytes (FGOs) show upregulation of WEE1 and pCDK1-Y15 (inactive CDK1) protein levels; treatment with WEE kinase inhibitor, PD166285, fully rescues the PN-arrest phenotype in oocytes and induces MII
• MASTL (microtubule associated serine/threonine kinase-like) protein is nearly undetectable in GV-stage FGOs but abundant in wild-type oocytes; microinjection of oocytes with Mastl mRNA partially rescues the PN-arrest leading to 50% higher numbers of MII-oocytes
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• first polar body emission (PBE) is significantly delayed (3-5 h)
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• following induction of superovulation, oocyte count is slightly but significantly lower than that in wild-type females
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• female mice are infertile when mated with adult wild-type C57BL/6J males for at least 8 months
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• no 2-cell, 4-cell, morula or blastocyst embryos are formed by ovulated oocytes after in vitro fertilization with wild-type sperm
• MII-stage oocytes rescued by the WEE kinase inhibitor, PD166285, can be fertilized in vitro by wild-type sperm and do form pronuclei; however, these pronucleus-stage embryos fail to cleave and develop further
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cellular
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• after in vitro fertilization with wild-type sperm, neither cleavage nor blastocyst formation are observed and oocytes gradually degenerate in culture
|
|
|
• consistent with a delay in anaphase I onset, ~73% of MI-oocytes stain positively for BUB1B (mitotic checkpoint serine/threonine kinase, aka BUBR1) expression at their kinetochores, indicating prolonged activation of the SAC
• however, oocytes show no alterations in the timing of meiotic progression to MI, the MI-spindle assembly and chromosome alignment, or microtubule attachment to kinetochores
|
|
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• a subset of LSM14B-bound mRNAs that are crucial for oogenesis show significantly decreased translational efficiency
|
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• most ovulated eggs (80%) exhibit a visible first polar body (PB1) and pronucleus (PN)
|
|
|
• oocytes fail to progress to metaphase II (MII); most ovulated eggs (80%) arrest at interphase with a prominent pronucleus (PN)-like internal structure, unlike wild-type ovulated eggs that arrest at MII
• metaphase I-to-anaphase I (MI-to-AI) transition and first polar body emission (PBE) are both significantly delayed (3-5 h) and activation of the spindle assembly checkpoint (SAC) is prolonged
• chemical inhibition of the TTK (MPS1) kinase by AZ3146 treatment to pass the SAC completely rescues the prolonged MI and delayed PBE defects
• prolonged MI and failed progression to MII are likely caused by delayed activation of the anaphase-promoting complex (APC) at the end of MI and an inability to reactivate maturation-promoting factor (MPF) after MI-to-AI transition
• GV-stage fully-grown oocytes (FGOs) show upregulation of WEE1 and pCDK1-Y15 (inactive CDK1) protein levels; treatment with WEE kinase inhibitor, PD166285, fully rescues the PN-arrest phenotype in oocytes and induces MII
• MASTL (microtubule associated serine/threonine kinase-like) protein is nearly undetectable in GV-stage FGOs but abundant in wild-type oocytes; microinjection of oocytes with Mastl mRNA partially rescues the PN-arrest leading to 50% higher numbers of MII-oocytes
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• first polar body emission (PBE) is significantly delayed (3-5 h)
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• a subset of LSM14B-bound mRNAs that are crucial for oogenesis show significantly decreased translational efficiency
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homeostasis/metabolism
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• a subset of LSM14B-bound mRNAs that are crucial for oogenesis show significantly decreased translational efficiency
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