Phenotypes Associated with This Genotype

Genotype
MGI:3841180

• Allelic Composition: Tg(Myh6-tTA)55Rbns/0; Tg(Myh6/tetO-PRKAG2*N488I)1Chib/0
• Genetic Background: Not Specified

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

cardiovascular system

increased cardiac muscle glycogen level ( J:145090 )

• myocardial glycogen content is 30-fold higher than in wild-type mice

• however, doxycycline treatment reduces myocardial glycogen content

abnormal heart morphology ( J:145090 )

• the anulus fibrosus that separates the atria from ventricles is discontinuous compared to in wild-type mice

• the anulus fibrosus in mice treated with doxycycline between 4 and 16 weeks is disrupted and disorganized without vacuolization of the septal and left ventricular wall myocytes

• however, the anulus fibrosus is intact in mice treated early with doxycycline (prenatal to 8 weeks)

abnormal myocardial fiber morphology ( J:145090 )

• unlike in wild-type mice, vacuoles are present in the myocytes of the right ventricle in mice treated with doxycycline between 4 and 16 weeks

heart left ventricle hypertrophy ( J:145090 )

• at 16 weeks

abnormal heart septum morphology ( J:145090 )

• hypertrophic at 8 weeks of age

increased heart weight ( J:145090 )

• heart weight is increased compared to in wild-type mice

• however, doxycycline treatment reduces heart weight 30% compared to in untreated mice

abnormal heart right ventricle morphology ( J:145090 )

• unlike in wild-type mice, vacuoles are present in the myocytes of the right ventricle in mice treated with doxycycline between 4 and 16 weeks

thick ventricular wall ( J:145090 )

• mice exhibit increased ventricular wall thickness compared to in wild-type mice

• early doxycycline treatment (prenatally to 8 weeks of age) delays myocardial wall thickening

• however, doxycycline treatment reduces ventricular wall thickness irregardless of treatment time

decreased heart left ventricle muscle contractility ( J:145090 )

• at 16 weeks, mice exhibit progressive systolic dysfunction indicated by increased left ventricle end diastolic diameter and decreased fractional shortening unlike wild-type mice

• however, doxycycline treatment ameliorates myocardial dysfunction

decreased heart rate ( J:145090 )

• mice exhibit decreased heart rates compared to in wild-type mice regardless of doxycycline treatment

increased heart rate ( J:145090 )

• 50% of mice frequently exhibit supraventricular tachycardia

• however, mice treated early (prenatal to 8 weeks) with doxycycline do not develop supraventricular tachycardia

abnormal impulse conducting system conduction ( J:145090 )

• mice exhibit preexcitation unlike in wild-type mice

• early doxycycline treatment (prenatally to 8 weeks of age) delays myocardial dysfunction

• doxycycline-treatment between 4 and 16 weeks results in a decline of preexcitation from 50% to 11% and is accompanied by atrial pacing

• doxycycline treatment after 8 weeks does not cause loss of preexcitation or alter the electrical properties of accessory pathways

• however, prenatal or early treatment with doxyxycline through 8 weeks of age prevents preexcitation while late treatment (after 20 weeks) improves cardiac conduction system function

• however, mice exhibit normal cardiac conduction velocity regardless of doxycycline treatment

shortened PR interval ( J:145090 )

• at 4 weeks, the PR interval is shortened in 50% to 60% of mice compared to in wild-type mice

atrioventricular block ( J:145090 )

• AV conduction properties are 50% prolonged compared to in wild-type mice

• 1 of 8 mice exhibited intermittent complete AV block

• early doxycycline suppression (prenatally to 8 weeks of age) does not improve sinus and atrioventriular node abnormalities

abnormal QRS complex ( J:145090 )

• at 4 weeks, 50% to 60% of mice exhibit prolonged, slurred-upstroke QRS complexes unlike in wild-type mice

prolonged QRS complex duration ( J:145090 )

sinoatrial block ( J:145090 )

• 30% of mice exhibit sinoatrial exit block unlike in wild-type mice

• early doxycycline suppression (prenatally to 8 weeks of age) does not improve sinus and atrioventriular node abnormalities

homeostasis/metabolism

increased cardiac muscle glycogen level ( J:145090 )

• myocardial glycogen content is 30-fold higher than in wild-type mice

• however, doxycycline treatment reduces myocardial glycogen content

muscle

increased cardiac muscle glycogen level ( J:145090 )

• myocardial glycogen content is 30-fold higher than in wild-type mice

• however, doxycycline treatment reduces myocardial glycogen content

abnormal myocardial fiber morphology ( J:145090 )

• unlike in wild-type mice, vacuoles are present in the myocytes of the right ventricle in mice treated with doxycycline between 4 and 16 weeks

heart left ventricle hypertrophy ( J:145090 )

• at 16 weeks

decreased heart left ventricle muscle contractility ( J:145090 )

• at 16 weeks, mice exhibit progressive systolic dysfunction indicated by increased left ventricle end diastolic diameter and decreased fractional shortening unlike wild-type mice

• however, doxycycline treatment ameliorates myocardial dysfunction

growth/size/body

heart left ventricle hypertrophy ( J:145090 )

• at 16 weeks

increased heart weight ( J:145090 )

• heart weight is increased compared to in wild-type mice

• however, doxycycline treatment reduces heart weight 30% compared to in untreated mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
lethal congenital glycogen storage disease of heart		DOID:0090101	OMIM:261740	J:145090