Mouse Genome Informatics
cx
    Tg(Myh6-tTA)55Rbns/0
Tg(Myh6/tetO-PRKAG2*N488I)1Chib/0

Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
cardiovascular system
• 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)
• 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
• hypertrophic at 8 weeks of age
• heart weight is increased compared to in wild-type mice
• however, doxycycline treatment reduces heart weight 30% compared to in untreated mice
• 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
• 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
• 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
• mice exhibit decreased heart rates compared to in wild-type mice regardless of doxycycline treatment
• 50% of mice frequently exhibit supraventricular tachycardia
• however, mice treated early (prenatal to 8 weeks) with doxycycline do not develop supraventricular tachycardia
• 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
• at 4 weeks, the PR interval is shortened in 50% to 60% of mice compared to in wild-type mice
• 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
• at 4 weeks, 50% to 60% of mice exhibit prolonged, slurred-upstroke QRS complexes unlike in wild-type mice
• 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
• myocardial glycogen content is 30-fold higher than in wild-type mice
• however, doxycycline treatment reduces myocardial glycogen content

muscle
• 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
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Glycogen Storage Disease of Heart, Lethal Congenital 261740 J:145090