Analysis Tools
behavior/neurological
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• water intake is decreased by 4 days after DOX removal
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• mice become hypoactive after DOX removal with a decrease in spontaneous activity evident in the light period by 1 week after DOX removal and in the dark period by 3 weeks after DOX removal
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• at 13 weeks of DOX removal, sleep/wake fragmentation is greatly increased
• during the dark period, the total time spend in wakefulness is reduced from 3 to 10 weeks after DOX removal
• at 1 week after DOX removal, transition frequency from wakefulness to slow-wave sleep is increased and this is further increased 4 weeks after DOX removal
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• the total time spent in REM sleep is decreased during the light period after 2 weeks of DOX removal and a trend toward reduced REM sleep is seen during the dark period
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• at one week after DOX removal, mice show fragmentation of wakefulness particularly in the early dark period
• the transition frequency between sleep/wake states is increased during the dark period between 1 and 13 weeks after DOX removal, but not in the light period
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narcolepsy
(
J:211045
)
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• at 13 weeks of DOX removal, sleep/wake fragmentation and cataplexy bout frequency are greatly increased, indicators of narcolepsy
• increase in cataplexy frequency is followed by a decrease in transitions to REM sleep
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hematopoietic system
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• IbaI-positive microglial cell number is increased in the lateral hypothalamic area by 2 weeks after DOX removal, indicating microglial cell activation
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immune system
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• IbaI-positive microglial cell number is increased in the lateral hypothalamic area by 2 weeks after DOX removal, indicating microglial cell activation
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muscle
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• cataplexy is seen as early as 2 weeks after DOX removal in both the dark and light periods and bout frequency increases from 2 to 11 weeks after DOX removal
• the time spent in cataplexy increases after 3 weeks of DOX removal during both the dark and the light periods
• mice kept on DOX-free chow from birth show lower number of cataplexy bouts than mice kept on DOX chow from birth and then DOX withdrawal for 13 weeks, indicating that ablation of orexin neurons in adulthood induces much more severe cataplexy episodes than ablation from birth
• cataplexy bout frequency is greater during the dark period and highest during the first half of the dark period and bout frequency tends to increase during the last 12 hours of light period
• cataplexy appears when about 95% of orexin neurons are lost
• mice fed chocolate after DOX removal at the beginning of the dark period show an increase in cataplexy bouts
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nervous system
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• IbaI-positive microglial cell number is increased in the lateral hypothalamic area by 2 weeks after DOX removal, indicating microglial cell activation
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• severe degeneration of orexin neurons is seen at 12 weeks of age in mice fed a DOX-free chow from birth
• mice raised on DOX chow show a decrease in the number of orexin neurons in the hypothalamus following doxycycline (DOX) removal such that by 2 weeks after DOX removal, about 95% of the orexin neurons are lost and by 11 weeks after DOX removal, orexin neurons decrease further to 1% of controls
• the number of orexin neurons rostral-caudally decreases uniformly after DOX removal, however, they decrease faster in the lateral hypothalamus than the medial population
• orexin neuron nerve endings in terminal fields in the locus ceruleus and dorsal raphe are decreased after DOX removal
• ablation of orexin neurons is arrested by DOX restoration and magnitude of neuron ablation is dependent on the duration of DOX removal
• however, the number of noradrenergic neurons, serotonergic neurons, and melanin-concentrating hormone-positive neuron are unaffected
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growth/size/body
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• body weight begins to increase shortly after DOX removal and is higher by 2 weeks after DOX removal, despite unaltered food consumption
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homeostasis/metabolism
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• insulin concentrations increase in mice at 4 weeks after DOX removal
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• leptin concentrations increase in mice at 4 weeks after DOX removal
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| narcolepsy | DOID:8986 |
OMIM:161400 OMIM:605841 OMIM:609039 OMIM:612417 OMIM:612851 OMIM:614223 OMIM:614250 |
J:211045 , J:211046 | |
