Phenotypes associated with this allele

• Allele Symbol: Trdnos^em1Ksng
• Allele Name: endonuclease-mediated mutation 1, Kunhua Song
• Allele ID: MGI:8240112
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Trdnos^em1Ksng/Trdnos^em1Ksng	C57BL/6J-Trdnos^em1Ksng	MGI:8240344

Genotype
MGI:8240344

hm1

• Allelic Composition: Trdnos^em1Ksng/Trdnos^em1Ksng
• Genetic Background: C57BL/6J-Trdnos^em1Ksng

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

mortality/aging

premature death ( J:364653 )

• although mice are born at expected Mendelian ratios, less than 20% of mice survive past 24 months of age versus >60% of wild-type controls

cardiovascular system

dilated heart left ventricle ( J:364653 )

• at 12 months of age, H&E analysis of transverse sections indicates only a slight dilation of the heart left ventricle

• however, overall adult heart anatomy and morphology are normal

decreased heart left ventricle muscle contractility ( J:364653 )

• at 8 months of age, mice show a slight decrease in the left ventricular ejection fraction relative to wild-type controls

irregular heartbeat ( J:364653 )

• mice are more susceptible to cardiac arrhythmias in response to catecholamine challenge with isoproterenol

• however, electrocardiographic parameters are normal in the absence of isoproterenol treatment

ventricular tachycardia ( J:364653 )

• mice show a significant increase in the duration of individual episodes of ventricular tachycardia (VT) during a 30-min period after intraperitoneal isoproterenol injection

ventricular premature beat ( J:364653 )

• mice show a significant increase in the rate of premature ventricular contractions (PVCs), expressed as times / 30 min, after intraperitoneal isoproterenol injection

abnormal myocardial fiber physiology ( J:364653 )

• isoproterenol-treated adult mouse cardiomyocytes (AMCMs) isolated from 5-mo-old mice show a significantly lower increase in the peak amplitude of Ca2+ transients than similarly treated wild-type AMCMs (+29% versus +44%)

• isoproterenol-treated caffeine-induced AMCMs exhibit a significantly higher sarcoplasmic reticulum (SR) Ca2+ content than similarly treated wild-type AMCMs

• overexpression of human cardiac triadin (Trisk32) in AMCMs by adenoviral delivery restores the amplitude of Ca2+ transients to the level in wild-type AMCMs after isoproterenol treatment

homeostasis/metabolism

impaired exercise endurance ( J:364653 )

• mice show a significant reduction in involuntary running distance in a treadmill endurance test

abnormal calcium ion homeostasis ( J:364653 )

• isoproterenol-treated adult mouse cardiomyocytes (AMCMs) isolated from 5-mo-old mice show a significantly lower increase in the peak amplitude of Ca2+ transients than similarly treated wild-type AMCMs (+29% versus +44%)

• isoproterenol-treated caffeine-induced AMCMs exhibit a significantly higher sarcoplasmic reticulum (SR) Ca2+ content than similarly treated wild-type AMCMs

• overexpression of human cardiac triadin (Trisk32) in AMCMs by adenoviral delivery restores the amplitude of Ca2+ transients to the level in wild-type AMCMs after isoproterenol treatment

decreased protein level ( J:364653 )

• qPCR analysis shows that expression of MT-1, the cardiac-predominant isoform produced by alternative splicing of the Trdn (triadin) gene, is downregulated by ~30% and 50% in adult hearts at 4- and 8 months of age, respectively, leading to a marked reduction in cardiac TRDN protein levels

• re-expression of Trdnos in AMCMs by adenoviral delivery normalizes MT-1 expression at both the mRNA and protein levels

behavior/neurological

impaired exercise endurance ( J:364653 )

• mice show a significant reduction in involuntary running distance in a treadmill endurance test

muscle

decreased heart left ventricle muscle contractility ( J:364653 )

• at 8 months of age, mice show a slight decrease in the left ventricular ejection fraction relative to wild-type controls

abnormal myocardial fiber physiology ( J:364653 )

• isoproterenol-treated adult mouse cardiomyocytes (AMCMs) isolated from 5-mo-old mice show a significantly lower increase in the peak amplitude of Ca2+ transients than similarly treated wild-type AMCMs (+29% versus +44%)

• isoproterenol-treated caffeine-induced AMCMs exhibit a significantly higher sarcoplasmic reticulum (SR) Ca2+ content than similarly treated wild-type AMCMs

• overexpression of human cardiac triadin (Trisk32) in AMCMs by adenoviral delivery restores the amplitude of Ca2+ transients to the level in wild-type AMCMs after isoproterenol treatment