Phenotypes for Tg(Myh6-Tnf)1.6Amf MGI:4450976 MGI Mouse

abnormal cardiovascular system morphology ( J:104759 )

increased heart left atrium size ( J:104759 )

• cross-sectional area is 2.6-fold larger than in wild-type mice

dilated heart atrium ( J:104759 )

increased heart weight ( J:104759 )

• at 6 to 9 months, the weight of the left atria is 3.6-fold greater than in wild-type mice

• mice exhibit increased heart to body weight compared with wild-type mice that is more severe in males and older mice

cardiac hypertrophy ( J:104759 )

• mice exhibit atrial and ventricular hypertrophy compared with wild-type mice

increased heart ventricle size ( J:104759 )

dilated heart ventricle ( J:104759 )

cardiac fibrosis ( J:104759 )

• males (at 10 weeks) and females (at 10 and 30 weeks) exhibit increased collagen deposition compared with wild-type mice

• percent fractional area with collagen is 10- to 20-fold higher than in wild-type mice

abnormal cardiovascular system physiology ( J:104759 )

dilated cardiomyopathy ( J:104759 )

decreased cardiac muscle contractility ( J:104759 )

• when stimulated with 1 Hz, total developed force and developed force normalized to cross-sectional area are 2.6-fold and 6.6-fold, respectively, compared to in similarly treated wild-type mice

• 6 Hz stimulation produces a 44% reduction of developed force with an increase in basal tension in the atria compared with 25% in similarly treated wild-type mice

decreased heart rate ( J:104759 )

• after 3 months, mice exhibit decreased heart rate compared with wild-type mice that is accentuated by lower heart rate in mice with chronic atrial fibrillation or flutter

irregular heartbeat ( J:104759 )

• 9 of 13 mice exhibit premature atrial beats unlike wild-type mice

• mice exhibit atrial arrhythmias with premature atrial beats and runs of atrial fibrillation or flutter unlike wild-type mice

• male mice exhibit a higher frequency of spontaneous and inducible atrial arrhythmias and a higher frequency of spontaneous premature atrial beats than female mice unlike wild-type mice

atrial fibrillation ( J:104759 )

• in 10 of 13 mice

abnormal impulse conducting system conduction ( J:104759 )

• upon single premature atrial stimuli, hearts exhibit slow atrial conduction and reentrant atrial tachycardias unlike similarly treated wild-type heart

• however, lowering the extracellular calcium ion concentration eliminates inducible atrial arrhythmias

abnormal atrioventricular node conduction ( J:104759 )

• older female mice exhibit with abnormal atrioventricular node (AVN) conduction with longer AVN Wenckebach periodicity and longer effective and functional refractory periods compared with wild-type mice

prolonged HV interval ( J:104759 )

• the HV intervals are prolonged and more horizontal cardiac electrical axes compared to in wild-type mice

• male mice exhibit longer HV intervals than female mice unlike wild-type mice

prolonged QRS complex duration ( J:104759 )

• male mice exhibit longer QRS than female mice unlike wild-type mice

prolonged QT interval ( J:104759 )

• mice exhibit prolonged QT intervals compared with wild-type mice

• young males exhibit prolonged PR intervals compared with wild-type mice

• male mice exhibit longer PR than female mice unlike wild-type mice

abnormal myocardial fiber physiology ( J:104759 )

• myocytes exhibit altered intracellular calcium ion activity and decreased sarcoplasmic reticulum calcium ion content compared with wild-type mice