Analysis Tools
mortality/aging
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• 20 of 31 mice survived to adulthood
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• 11 of 31 mice died within 48 hours after birth; remaining 20 survived to adulthood
• mice were significantly underrepresented at P26
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growth/size/body
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• mice were smaller than wild-type controls at weaning time
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• body weight was significantly decreased in males (from P4 to P21) and females (from P2 to P21)
• both sexes maintained significantly reduced body weight at 4, 8 and 12 weeks of age
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• both sexes showed stunted postnatal somatic growth
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homeostasis/metabolism
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• at 7.5 dpc, the average serum 17beta-estradiol concentration was only 50% of that in wild-type females
• serum levels of 17beta-estrodiol were significantly lower than in wild-type females at 40 hrs post pregnant mare serum gonadotropin (PMSG) treatment and at 24 hrs post human chorionic gonadtropin (hCG) treatment
• however, Cyp19a1 expression in the ovaries was normal
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• mice showed a 36% reduction in serum IGF-1 levels relative to wild-type controls; however, mRNA levels in the liver were relatively normal
• mice exhibited faster human IGF-1 degradation in the blood circulation than wild-type controls
• both IGFBP-3 mRNA expression in the kidney and serum IGFBP-3 levels were significantly reduced resulting in IGF-1 destabilization
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reproductive system
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N |
• females exhibited normal timing of vaginal opening
• sexually mature females showed normal ovarian and uterus histology
• 17beta-estradiol treatment stimulated robust growth of uteri in ovariectomized females
• treatment of 17beta-estradiol + progesterone blunted the 17beta-estradiol-induced uterine growth in ovariectomized females, suggesting normal progesterone signaling in the uterus
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• oocytes exhibited abnormal shapes and rough edges
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• females showed significantly increased levels of H3K9me1, H3K9me2 and H3K9me3 in the ovary and uterus
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• at 1.5 dpc, 4 of 5 examined females only discharged an average of 4.6 oocytes per mouse versus 8.4 oocytes in wild-type females
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• remaining 1 of 6 adult females studied stayed at the diestrus phase for 12 days
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• 3 of 6 adult females exhibited prolonged estrous cycles
• only 2 of 6 examined females showed normal estrous cycles
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• after successful coitus, females exhibited a lower pregnancy rate and carried fewer embryos at 4.5 and 7.5 dpc than pregnant wild-type controls
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• estrogen-primed, progesterone-dependent and mechanically-induced decidualization was significantly reduced, as the average weight of scratched uterine horns was only 1.5-fold of that in unscratched horns
• alkaline phosphotase activity was induced at much lower degrees in scratched uterine horns relative to that in wild-type controls
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• embryonic implantation sites were fewer and smaller than those in wild-type uteri
• at 4.5 and 7.5 dpc, most implanted embryos were either small or were being absorbed
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• females are largely infertile; four breeding pairs of mutant females and wild-type males failed to produce any offspring
• over a 4-month period, only one female delivered three pups, but these pups died shortly after birth
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• at 1.5 dpc, only 43% of oocytes were fertilized versus ~81% of oocytes in wild-type females
• following induction of superovulation by PMSG and hCG treatment, the fertilization rate was only 8%, almost 7-fold lower than that in wild-type controls
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behavior/neurological
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• mice were less active than wild-type controls at weaning time
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embryo
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• estrogen-primed, progesterone-dependent and mechanically-induced decidualization was significantly reduced, as the average weight of scratched uterine horns was only 1.5-fold of that in unscratched horns
• alkaline phosphotase activity was induced at much lower degrees in scratched uterine horns relative to that in wild-type controls
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cellular
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• oocytes exhibited abnormal shapes and rough edges
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