Phenotypes Associated with This Genotype

Genotype
MGI:3626205

• Allelic Composition: Nhlh1^tm1Irk/Nhlh1^tm1Irk
• Genetic Background: involves: 129S4/SvJae

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

mortality/aging

premature death ( J:78031 )

• adult homozygotes are viable, fertile and overtly healthy with no evidence of epilepsy, myocardial infarction or CNS, skeletal or cardiac morphological abnormalities; however, ~25% of homozygotes die by 1 year of age, probably due to a predisposition to ventricular arrhythmias

cardiovascular system

decreased heart rate variability ( J:78031 )

• at 10 and 12 months of age, homozygotes display a significant reduction in total heart rate power (an index of heart rate variability) relative to wild-type mice (14.2 1.96 ms² vs 31.7 6.11 ms², respectively)

• in addition, homozygotes exhibit a slight increase in the low-frequency-to-high-frequency heart rate variability ratio relative to wild-type mice (2.23 0.653 vs 1.16 0.166, respectively), suggesting reduced parasympathetic activation

irregular heartbeat ( J:78031 )

• in response to sudden water immersion, homozygotes fail to exhibit a transient diving-induced bradycardia, indicating absence of a vagal response; an increased heart rate (644 40 bpm vs 569 34 bpm in wild-type) is observed for the first 30 beats after immersion

ventricular premature beat ( J:78031 )

• in response to swimming stress, ECGs from homozygotes exhibit premature ventricular complexes, couplets, and triplets during swimming while wild-type ECGs show only isolated ventricular escape beats during ""diving""-induced atrioventricular block

abnormal QT variability ( J:78031 )

• at 10 and 12 months of age, homozygotes show no differences in mean QT interval or heart rate-corrected QT interval [QT_c] relative to wild-type mice, indicating absence of a long QT syndrome

• however, homozygotes display a significantly higher, positive number in the QT variability index (normally a unitless negative number) than wild-type mice (0.17 0.142 vs -0.39 0.176, respectively), indicating increased repolarization lability

nervous system

abnormal parasympathetic nervous system physiology ( J:78031 )

• homozygotes exhibit a decreased total heart rate variability, a reduced diving reflex, and impaired baroreceptor sensitivity, indicating a functional parasympathetic deficit in the absence of heart structural abnormalities

• in contrast, sympathetic activity appears unaffected, as measured by total beta-adrenergic receptor density in myocardial membranes