mortality/aging
• over time, mutants show an increase in spontaneous deaths, with more than 30% of mutants under 24 weeks of age dying
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• over time, mutants show an increase in spontaneous deaths, with more than 30% of mutants under 24 weeks of age dying
• death is sudden with no signs of weight loss, dehydration, or abnormal posture
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• fewer than the expected numbers (23.3% vs. 29% expected) of homozygotes are seen at weaning, indicating some loss either during embryonic development or early postnatal life
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reproductive system
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• mice exhibit preterm labor prior to day 19.6 of pregnancy compared with wild-type mice
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behavior/neurological
• mutants show no hypothermia, no hypoactivity, and no catalepsy after administration of HU210, a potent synthetic cannabinoid agonist or delta9-tetrahydrocannabinol (THC) and no delta9-THC-induced analgesia in the hotplate test
• mutants exhibit head bobbing, assume a hunched position after injection, lick their abdomens, and have strong diarrhea after delta9-THC injection, unlike wild-type which show pronounced hypoactivity
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• rearing rate is reduced drastically
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• mutants are hypoactive in the open-field test
(J:54995)
• mutants exhibit a reduction in locomotor activity, in both ambulation counts and ambulation time
(J:55294)
• however, motor coordination on the rotarod appears normal
(J:55294)
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hypoalgesia
(
J:54995
)
• hypoalgesia in hotplate and formalin tests
• responses are normal in the tail-flick test
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• mutants show a reduced number of pain responses in the early phase of the formalin test
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• mutants show increased response latencies in the hotplate test
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• mutants spend longer time motionless in the ring catalepsy test compared to wild-type indicating an increase in ring catalepsy
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homeostasis/metabolism
• on days 16 to 19 of pregnancy
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• on days 14 to 16 of pregnancy
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• on day 19 of pregnancy
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• during late pregnancy
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cellular
• newborns exhibit reduced birth weights compared to wild-type mice or newborns from homozygous females mated with wild-type mice
• however, treatment with a CRH-RI selective antagonist, antalarmin hydrochloride, on days 15 to 17 of pregnancy or progesterone on day 18 of pregnancy restores normal birth weights
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