reproductive system
N |
• double mutant Sertoli cells exhibit normal phagocytosis of apoptotic spermatogenic cells relative to wild-type controls, as determined by lipid droplet formation using Oil Red O staining
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• defects less severe than in mice homozygous for both Mertktm1Grl and Tyro3tm1Grl
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• first estrus, which is dependent on a normal GnRH-induced LH surge mechanism, is delayed
• in contrast, onset of vaginal opening is normal
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• double homozygous females display a delayed first estrus by 4 days relative to wild-type controls
• however, double homozygous females are fertile and deliver healthy litters of normal-size pups
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• at 2 months of age, many double homozygous females exhibit decreased diestrous phase lengths relative to wild-type controls
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• at 2 months of age, many double homozygous females spend more than twice as much time in proestrus than wild-type controls
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• at 2-, 4-, and 6 months of age, double homozygous females exhibit prolonged irregular estrous cycle lengths, averaging ~2 to 3 times longer than those of age-matched wild-type controls
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endocrine/exocrine glands
immune system
cellular
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• double homozygous females exhibit increased cell death in the nose and dorsal forebrain relative to wild-type controls
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• at E15, caspase 3 cleavage analysis revealed a 1.8-fold increase in the number of apoptotic cells in the dorsal forebrain, consistent with the location of loss of GnRH neurons number during migration
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• at E15, double homozygous females show a 36% deficit in the appropriate targeting and positioning of GnRH neurons in the ventral forebrain
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nervous system
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• at E15, caspase 3 cleavage analysis revealed a 1.8-fold increase in the number of apoptotic cells in the dorsal forebrain, consistent with the location of loss of GnRH neurons number during migration
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• at E15, double homozygous females show a 36% deficit in the appropriate targeting and positioning of GnRH neurons in the ventral forebrain
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• at 2 months of age, double homozygous females show a 24% decrease in the total number of gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus relative to wild-type controls
• a more striking deficit (34%) of GnRH neurons is noted in regions surrounding the organum vasculosum of the lamina terminalis (OVLT), known to be critical for the GnRH-induced LH surge
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• at E15, double mutant brains show a striking loss (36%) of GnRH-immunoreactive cells within the context of ventral forebrain but not more rostrally
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