Phenotypes associated with this allele

• Allele Symbol: Scn5a^tm1Clhh
• Allele Name: targeted mutation 1, Christopher LH Huang
• Allele ID: MGI:3765977
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Scn5a^tm1Clhh/Scn5a^tm1Clhh	involves: 129 * 129S/SvEv * C57BL/6J	MGI:3765986
ht2	Scn5a^tm1Clhh/Scn5a^+	involves: 129 * 129S/SvEv * C57BL/6J	MGI:3765987
ht3	Scn5a^tm1Clhh/Scn5a^+	involves: 129/SvEv	MGI:5582068

Genotype
MGI:3765986

hm1

• Allelic Composition: Scn5a^tm1Clhh/Scn5a^tm1Clhh
• Genetic Background: involves: 129 * 129S/SvEv * C57BL/6J

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

mortality/aging

prenatal lethality, complete penetrance ( J:127879 )

• mice begin to die at E10.5 and none are born

embryo

decreased embryo size ( J:127879 )

• at E10.5, 2 of 5 mice are smaller than wild-type

embryo tissue necrosis ( J:127879 )

• at E10.5, all embryos exhibit necrosis compared to no wild-type mice

cardiovascular system

irregular heartbeat ( J:127879 )

• at E10.5, 1 of 5 mice exhibited an irregular heartbeat

growth/size/body

decreased embryo size ( J:127879 )

• at E10.5, 2 of 5 mice are smaller than wild-type

Genotype
MGI:3765987

ht2

• Allelic Composition: Scn5a^tm1Clhh/Scn5a⁺
• Genetic Background: involves: 129 * 129S/SvEv * C57BL/6J

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:127879 )

• following tail clipping one mouse exhibited generalized seizure and died

• however, the lifespan of other mice is normal

postnatal lethality, incomplete penetrance ( J:127879 )

• fewer than expected mice are recovered 3 to 4 weeks after birth

cardiovascular system

ventricular tachycardia ( J:127879 )

• unlike in wild-type mice, application of programmed electrical stimulation induced ventricular tachycardia in 8 of 9 mice

irregular heartbeat ( J:127879 )

• electrogram duration (EGD) during programmed electrical stimulation parallels (PES) arrhythmic tendencies

• unlike in wild-type mice, propranolol fails to suppress arrhythmias following treatment with isoproterenol

• isoproterenol does not affect arrhythmia status during PES whereas in wild-type mice it induces arrhythmic effects

• mexiletine suppresses arrhythmias in 4 of 5 mice without effecting EGD

abnormal impulse conducting system conduction ( J:127879 )

• hearts exhibit greater increases in electrogram duration (EGD) than wild-type hearts during programmed electrical stimulation (PES)

• EGD during PES parallels arrhythmic tendencies

• mice exhibit greater stimulus to response latencies measured at the beginning of the PES sequences than do wild-type mice

• mice exhibit larger ventricular effective refractory period than wild-type mice (37+/-7 msec compared to 29+/-6 msec)

• unlike in wild-type mice, 1 uM propranolol accentuates the increase in EGD as S1S2 intervals are shortened

• treatment with propranolol increases EGD

abnormal myocardial fiber physiology ( J:127879 )

• action potential is prolonged in myocytes (152+/-17.8 msec compared to 55+/-6.6 msec in wild-type cells)

• unlike in wild-type mice, myocytes exhibit early afterdepolarization and persistent sodium tail currents

behavior/neurological

seizures ( J:127879 )

• following tail clipping one mouse exhibited generalized seizure and died

nervous system

seizures ( J:127879 )

• following tail clipping one mouse exhibited generalized seizure and died

Genotype
MGI:5582068

ht3

• Allelic Composition: Scn5a^tm1Clhh/Scn5a⁺
• Genetic Background: involves: 129/SvEv

cardiovascular system

sinus bradycardia ( J:186583 )

• 6 of 10 mice under ketamine anesthesia show sinus bradycardia after pacing

abnormal impulse conducting system conduction ( J:186583 )

• electrocardiographic waveforms suggest depressed intra-atrial, atrioventricular node, and intraventricular conduction in the absence of sinoatrial exit block

• sinatrial preparations show depressed sinus rate, greater excitation latencies and slowed conduction velocities for the spread of excitation between the sinoatrial node and atrial septum

abnormal atrioventricular node conduction ( J:186583 )

• electrocardiographic waveforms suggest slow atrioventricular node conduction

atrioventricular block ( J:186583 )

• 4 of 10 mice under ketamine anesthesia show II to III atrioventricular block

prolonged PR interval ( J:186583 )

• mice under avertin anesthesia show longer PR intervals

prolonged QRS complex duration ( J:186583 )

• mice under avertin anesthesia show longer QRS durations

prolonged QT interval ( J:186583 )

• mice under avertin anesthesia show abnormal ventricular repolarization, seen as increased QT and corrected QT intervals (after correction for RR intervals) compared with wild-type mice

abnormal sinoatrial node conduction ( J:186583 )

• mice under ketamine or avertin anesthesia exhibit greater sinus node recovery times after a burst pacing protocol over a 30-second stimulation period, indicating depressed sinoatrial node pacemaker function

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
long QT syndrome 3		DOID:0110646	OMIM:603830	J:186583