behavior/neurological phenotype

• abnormal eye blink conditioning behavior
  • a deficiency was observed in latency to peak conditioned response
  (MGI Ref ID J:86763)

• abnormal spatial learning
  • impaired learning in a water maze test
  (MGI Ref ID J:86763)

• abnormal motor learning
  • impairment apparently involves learning and memory of relatively fast coordinated movements
  (MGI Ref ID J:86763)
  • there is a learned motor skill deficit in a rotorod test
  (MGI Ref ID J:86763)

• abnormal learning/memory/conditioning
  (MGI Ref ID J:86763)

• increased thigmotaxis
  • observed during water maze tests
  (MGI Ref ID J:86763)

mammalian phenotype

• behavior/neurological phenotype
  • Normal - basic motor functions were all normal
  (MGI Ref ID J:86763)
  • basic mnotor functions were all normal
  (MGI Ref ID J:86763)

nervous system phenotype

• abnormal action potential
  • Normal - however, early repolarization is normal
  (MGI Ref ID J:188823)
  • during late polarization, epicardial ventricular myocyte action potentials are shorter than in wild-type cells
  (MGI Ref ID J:188823)

cardiovascular system phenotype

• abnormal myocardial fiber physiology
  • during late polarization, epicardial ventricular myocyte action potentials are shorter than in wild-type cells
  (MGI Ref ID J:188823)
  • Normal - however, early repolarization is normal
  (MGI Ref ID J:188823)

cardiovascular system phenotype

• abnormal heartbeat
  • mice exhibit congenital sinus node dysfunction characterized by bradycardia, sinus dysrhythmia, prolonged sinoatrial node recovery time, increased sinoatrial conduction time, and recurrent sinus pauses
  (MGI Ref ID J:219164)
  • Normal - however, echocardiographic analysis indicates normal cardiac structure, diastolic function, and systolic function and cardiac morphology
  (MGI Ref ID J:219164)

• abnormal RR interval
  • dramatic fluctuations of the RR interval; fluctuations in RR interval are more pronounced during phases of slow heart rate
  (MGI Ref ID J:219164)

• abnormal sinoatrial node conduction
  • atrial pacing (continuously for 10 seconds at 10 Hz) of isolated right atrial preparation containing the sinoatrial node indicates an increase in sinus node recovery time
  (MGI Ref ID J:219164)
  • Normal - however, atrioventricular conduction is normal
  (MGI Ref ID J:219164)
  • intracardiac electrophysiological analysis indicates increased sinus node recovery time, indicating a delayed impulse formation within the sinoatrial node
  (MGI Ref ID J:219164)
  • isolated central pacemaker cells, both spindle cells and elongated cells, show reduced amplitude of I(f) current in response to hyperpolarizing voltage steps and slowing of the activation kinetics of I(f) current
  (MGI Ref ID J:219164)

• increased heart rate variability
  • mutants exhibit an increase in heart rate variability
  (MGI Ref ID J:219164)
  • intact sinoatrial node preparations exhibit pronounced fluctuations of the beat-to-beat interval
  (MGI Ref ID J:219164)

• sinus bradycardia
  • bradycardia is not due to an increase in resting phases because mutants exhibit the same activity and resting behavior as wild-type mice
  (MGI Ref ID J:219164)
  • in vivo telemetric long-term ECG in freely moving mutants and echocardiographic analysis indicates a sinus bradycardia characterized by lower mean heart rates by 16% compared to wild-type and more frequent episodes of low heart rate
  (MGI Ref ID J:219164)
  • intact sinoatrial node preparations show a reduced firing rate of spontaneous pacemaker potentials by 29% compared with wild-type
  (MGI Ref ID J:219164)
  • isolated perfused hearts exhibit a reduction in beating rate by 20.2%
  (MGI Ref ID J:219164)
  • isolated sinoatrial pacemaker cells show a shifted resting membrane potential to more hyperpolarized potentials, and a reduced firing rate (by 13%), indicating reduced beating frequency
  (MGI Ref ID J:219164)
  • beta-adrenergic stimulation with isoproterenol results in the same relative increase in heart rate as in wild-type mice, however the maximum heart rate is lower in mutants
  (MGI Ref ID J:219164)

• sinoatrial block
  • premature atrial stimulation indicates a prolonged sinoatrial conduction time independent of changes in sinus cycle lengths, indicating impaired impulse propagation and sinoatrial exit block
  (MGI Ref ID J:219164)

• decreased cardiac output
  • Normal - however, stroke volume is normal
  (MGI Ref ID J:219164)
  • reduction in cardiac output to 69% of wild-type
  (MGI Ref ID J:219164)

behavior/neurological phenotype

• abnormal depression-related behavior
  • mice exhibit less time immobile in forced swim and tail suspension tests compared with wild-type mice
  (MGI Ref ID J:173355)