Phenotypes associated with this allele

• Allele Symbol: Hcrt^tm1Ywa
• Allele Name: targeted mutation 1, Masashi Yanagisawa
• Allele ID: MGI:2151182
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hcrt^tm1Ywa/Hcrt^tm1Ywa	B6.129S6-Hcrt^tm1Ywa	MGI:3763456
hm2	Hcrt^tm1Ywa/Hcrt^tm1Ywa	involves: 129S6/SvEvTac	MGI:4949137
hm3	Hcrt^tm1Ywa/Hcrt^tm1Ywa	involves: 129S6/SvEvTac * C57BL/6	MGI:3763455
ht4	Hcrt^tm1Ywa/Hcrt^+	involves: 129S6/SvEvTac * C57BL/6	MGI:3767399

Genotype
MGI:3763456

hm1

• Allelic Composition: Hcrt^tm1Ywa/Hcrt^tm1Ywa
• Genetic Background: B6.129S6-Hcrt^tm1Ywa

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

behavior/neurological

decreased locomotor activity ( J:111673 )

• dark phase activity significantly reduced

abnormal sleep pattern ( J:111673 )

• periods of wakefulness not significantly reduced

• periods of wakefulness much more fragmented

• loss of rhythmicity to periods of wakefulness

fragmentation of sleep/wake states ( J:111673 )

homeostasis/metabolism

abnormal circadian temperature homeostasis ( J:111673 )

• loss of rhythmicity in body temperature fluctuations

• drop in body temperature while resting is much less than in controls

• core body temperature is higher during dark phase and normal in light phase

Genotype
MGI:4949137

hm2

• Allelic Composition: Hcrt^tm1Ywa/Hcrt^tm1Ywa
• Genetic Background: involves: 129S6/SvEvTac

behavior/neurological

abnormal gait ( J:83817 )

• gait disturbances immediately precede 42% of abrupt arrests in activity during a narcoleptic episode, but never precede gradual arrests

abnormal sleep pattern ( J:83817 )

• wakefulness is disrupted, with mice showing higher frequencies of awake episodes during the light and dark phases and severely diminished durations of wakefulness episodes over the entire dark phase

abnormal non-rapid eye movement sleep pattern ( J:83817 )

• non-REM sleep is disrupted, with mice showing higher frequencies of non-REM sleep episodes during the dark phase and a reduction in durations of non-REM sleep, especially at night

abnormal paradoxical sleep pattern ( J:83817 )

• mice show a reduced mean interval between REM sleep episodes during the dark phase and reduced latencies to REM sleep during both phases

increased frequency of paradoxical sleep ( J:83817 )

• 75% increase in the amount of time in REM sleep over the entire dark period and a compensatory reduction during the light phase

fragmentation of sleep/wake states ( J:170824 )

• wake and non-REM sleep bouts are shorter and more frequent

narcolepsy ( J:83817 )

• episodes of abrupt cessation of purposeful activity and spontaneous transitions directly to cataplexy-like attacks of REM sleep with atonia or more rarely, of non-REM sleep in the pre-REM stage with atonia

• mice also show episodes of gradual cessation of purposeful activity and a transition to non-REM sleep

• abrupt arrests are associated with emotive motor activity such as vigorous grooming, ambulation, and climbing, while gradual arrests are preceded by quiet wakefulness

• gradual arrests are occasionally accompanied by automatic behavior such as stereotypic continued chewing of food after the onset of non-REM sleep

• 38% of gradual arrests initiate with non-REM sleep but progress rapidly to REM sleep

• treatment with the anticataplectic agent clomipramine decreases the frequency of abrupt arrests but does not affect gradual arrests, while treatment with clomipramine and caffeine results in suppression of both abrupt and gradual arrests

muscle

abnormal muscle tone ( J:170824 )

• frequent cataplexy

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:83817

Genotype
MGI:3763455

hm3

• Allelic Composition: Hcrt^tm1Ywa/Hcrt^tm1Ywa
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

behavior/neurological

abnormal posture ( J:57124 )

• sudden sustained changes in posture which end when activity resumes

• 8-27 episodes in a 4 hour period averaging about 66 seconds in length

abnormal locomotor behavior ( J:57124 )

abnormal locomotor activation ( J:57124 , J:85405 )

• side to side rocking motion in about 75% of behavior arrest episodes (J:57124)

• less affected by intruders (J:85405)

abnormal gait ( J:57124 )

• ataxic gait appears 1-3 sec before episodes of behavior arrest in about 27% of cases

increased vertical activity ( J:57124 )

• burrowing and climbing activity frequently precede posture change

behavioral arrest ( J:57124 )

• frequent periods of behavioral arrest at night when mice are most active

• sudden collapse of head and neck and body falls to the cage floor

• episodes more frequent and begin earlier when mice are housed in groups

• often preceded by chasing, tail biting and social grooming

decreased locomotor activity ( J:85405 )

• dark phase activity significantly reduced

narcolepsy ( J:57124 )

• shortened REM sleep latency during light phase

• increased time and duration of REM sleep during dark phase

• decreased time between REM episodes

• increased non REM sleep time

• decreased awake time and shorter duration of awake episodes

cardiovascular system

increased heart rate ( J:85405 )

• ephemeral increase at low doses

• less effect of intruders

abnormal systemic arterial blood pressure ( J:85405 )

• less affected by intruders

• less affected by hexamethonium and prazosin

decreased mean systemic arterial blood pressure ( J:85405 )

• significantly reduced

• bicucullin stimulation ineffective at very low doses and of shorter duration at higher dose

respiratory system

increased pulmonary respiratory rate ( J:85405 )

• respiratory frequency is significantly increased

nervous system

abnormal nervous system electrophysiology ( J:85405 )

• effect of bicucullin on EEG is of short duration even at higher doses

growth/size/body

increased susceptibility to age related obesity ( J:128233 )

• female but not male mice over 100 days in age have significant increases in body weight compared to littermate controls

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:57124

Genotype
MGI:3767399

ht4

• Allelic Composition: Hcrt^tm1Ywa/Hcrt⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

growth/size/body

increased susceptibility to age related obesity ( J:128233 )

• female but not male mice over 100 days in age have significant increases in body weight compared to wild-type mice but not as great as in homozygote mice