Phenotypes associated with this allele

• Allele Symbol: Scn5a^tm1Agrc
• Allele Name: targeted mutation 1, Andrew A Grace
• Allele ID: MGI:2179753
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Scn5a^tm1Agrc/Scn5a^tm1Agrc	involves: 129 * C57BL/6J	MGI:3621904
ht2	Scn5a^tm1Agrc/Scn5a^+	involves: 129	MGI:3641169
ht3	Scn5a^tm1Agrc/Scn5a^+	involves: 129 * C57BL/6J	MGI:3621905

Genotype
MGI:3621904

hm1

• Allelic Composition: Scn5a^tm1Agrc/Scn5a^tm1Agrc
• Genetic Background: involves: 129 * C57BL/6J

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

Morphology of E10.5 control and Scn5a^tm1Agrc/Scn5a^tm1Agrc hearts

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:76331 )

• observe no heart contractions beyond E11.5 and see autolysis of embryos

cardiovascular system

decreased myocardial fiber number ( J:76331 )

• reduction in the number of thin, spindle-like cardiomyocytes

abnormal heart ventricle morphology ( J:76331 )

• reduction in chamber size, however, the endocardial cushions of the atrioventricular canal, the common atrial chamber, and the truncus arteriosus all appear normal

abnormal trabecula carnea morphology ( J:76331 )

• reduction in trabeculation of the ventricular wall

abnormal cardiac muscle contractility ( J:76331 )

• show uncoordinated contractions at E10.5

embryo

decreased embryo size ( J:76331 )

• smaller at E10.5

growth/size/body

decreased embryo size ( J:76331 )

• smaller at E10.5

muscle

decreased myocardial fiber number ( J:76331 )

• reduction in the number of thin, spindle-like cardiomyocytes

abnormal trabecula carnea morphology ( J:76331 )

• reduction in trabeculation of the ventricular wall

abnormal cardiac muscle contractility ( J:76331 )

• show uncoordinated contractions at E10.5

Genotype
MGI:3641169

ht2

• Allelic Composition: Scn5a^tm1Agrc/Scn5a⁺
• Genetic Background: involves: 129

cardiovascular system

cardiac fibrosis ( J:109689 )

• old but not young mutants show extensive fibrosis of the ventricular myocardium (in the left and right ventricular free walls and in the interventricular septum)

• although young mutants do not exhibit ventricular fibrosis, they do show increased perivascular fibrosis which becomes massive with age

decreased heart rate ( J:109689 )

• show slight but significant bradycardia

ventricular tachycardia ( J:166438 )

• mutants exhibit a higher incidence of ventricular tachycardia than wild-type (25% vs. 6%)

• ventricular tachycardias begin at earlier times in the right ventricular outflow tract than at the base of the left ventricle

• mutant hearts exhibit abnormal electrophysiological properties of the right ventricle at the right ventricle outflow tract, showing increased heterogeneities in action potential duration, ventricular effective refractory periods, electrogram duration ratios and response latencies that correlate with an increased incidence of discordant alternans and with steeper restitution slopes

abnormal impulse conducting system conduction ( J:109689 )

prolonged PR interval ( J:109689 )

• PR intervals progressively prolong with age (from 3 to 71 weeks)

prolonged P wave ( J:109689 )

• P-wave intervals progressively prolong with age (from 3 to 71 weeks)

prolonged QRS complex duration ( J:109689 )

• QRS intervals progressively prolong with age (from 3 to 71 weeks)

prolonged QT interval ( J:109689 )

• QTrc and QTc intervals are prolonged due to prolongation of the QRS interval

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Brugada syndrome 1		DOID:0110218	OMIM:601144	J:166438
progressive familial heart block type IA		DOID:0111074	OMIM:113900	J:109689

Genotype
MGI:3621905

ht3

• Allelic Composition: Scn5a^tm1Agrc/Scn5a⁺
• Genetic Background: involves: 129 * C57BL/6J

cardiovascular system

abnormal heart rate ( J:76331 )

• after aortic cannulation and Langendorff-perfusion, whole isolated hearts show marked rate slowing

ventricular tachycardia ( J:76331 )

• display ventricular tachycardia during continuous pacing or after the delivery of S2 stimuli at shorter S1-S2 intervals

abnormal impulse conducting system conduction ( J:76331 )

• exhibit a 50% reduction in sodium conduction, leading to impaired action potential propagation and atrioventricular conduction, delayed intramyocardial conduction, increased ventricular refractoriness, and ventricular tachycardia with characteristics of reentrant excitation

prolonged PR interval ( J:76331 )

• prolonged PR interval, however QT interval is unchanged

prolonged P wave ( J:76331 )

abnormal myocardial fiber physiology ( J:76331 )

• peak current densities of myocytes are reduced, indicating reduced sodium channel density

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
progressive familial heart block type IA		DOID:0111074	OMIM:113900	J:76331