Phenotypes Associated with This Genotype

Genotype
MGI:5575895

• Allelic Composition: Tg(Myh6-KCNQ1_i2)H05Desc/0
• Genetic Background: involves: FVB

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

cardiovascular system

abnormal heart morphology ( J:211437 )

• cardiac sodium channel remodeling/upregulation that occurs before the onset of cardiac hypertrophy

cardiac hypertrophy ( J:211437 )

• cardiac hypertrophy, including increases in myocardial cross-section, with no differences in cell proliferation is seen at E18.5, but not at E14.5

abnormal cardiovascular system physiology ( J:211437 )

• sodium current recordings show that peak current densities are 30-40% higher in ventricular myocytes, a 30-40% higher conductance, and slower recovery time from inactivation

• while wild-type ventricles have a predominately left-right activation pattern (94%) at E18.5, mutant hearts maintain a left ventricular activation pattern (84%), indicating abnormal ventricular activation pattern during development

• under spontaneous rhythm, mice show an increase in total left ventricular activation time at E18.5 and in adults, but not at E14.5, indicating a delay in the transmission of the electrical impulse

• however, under stimulated contraction, no differences in left ventricular activation time at any age are seen, indicating that electrical impulse transmission through the working myocardium is not altered

abnormal impulse conducting system conduction ( J:211437 )

• sodium current recordings from ventricular myocytes show a 30-40% higher conductance

prolonged QT interval ( J:132483 , J:211437 )

• QT interval prolongation, although to a lesser extent than in transgenic lines H08 or H02 (J:132483)

abnormal T wave ( J:132483 )

• the rapid component of the T wave is slightly prolonged

abnormal sinoatrial node conduction ( J:132483 )

• sinus node dysfunction as indicated by a longer intrinsic sinus period under autonomic nervous blockade and an increase in minimum sinus period under isoproterenol infusion, although to a lesser extent than in transgenic lines H08 or H02

prolonged P wave ( J:132483 )

• longer P wave duration than in wild-type mice, although to a lesser extent than in transgenic lines H08 or H02

• however, PR interval duration is similar to wild-type mice

mortality/aging

decreased survivor rate ( J:211437 )

• lower survival rate at 1 year of age

premature death ( J:211437 )

• lower survival rate at 1 year of age

growth/size/body

cardiac hypertrophy ( J:211437 )

• cardiac hypertrophy, including increases in myocardial cross-section, with no differences in cell proliferation is seen at E18.5, but not at E14.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
long QT syndrome 1		DOID:0110644	OMIM:192500	J:211437