Phenotypes Associated with This Genotype

Genotype
MGI:5432113

• Allelic Composition: Gt(ROSA)26Sor^tm1(DTA)Jpmb/Gt(ROSA)26Sor⁺; Hcn4^{tm1(cre/ERT2)Anlu}/Hcn4⁺
• Genetic Background: involves: 129S/SvEv

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

mortality/aging

premature death ( J:186021 )

• approximately 20% of mice die suddenly with no ante-mortem indication of illness within 60 days after high dose tamoxifen treatment

cardiovascular system

abnormal sinoatrial node morphology ( J:186021 )

• ablation of sinoatrial node cells following tamoxifen treatment that varies depending on tamoxifen dose

cardiac fibrosis ( J:186021 )

• tamoxifen induced ablation of sinoatrial node cells is accompanied by a destructive fibrosis of nodal tissue

increased heart rate variability ( J:186021 )

• following 5 days of tamoxifen treatment show alternating periods of slow and fast frequencies in R-R tachograms

• alterations of long electrical standstills (sinus pauses) and intermittent rapid atrial activity following tamoxifen treatment

• following 5 days of tamoxifen treatment absolute value of the maximally (isoprenaline) stimulated heart rate remained low

decreased heart rate ( J:186021 )

• following 5 days of high or low dose tamoxifen treatment heart rate falls by about 40 - 50% or 12%, respectively

irregular heartbeat ( J:186021 )

• variety of cardiac rhythm disturbances; including sino-atrial arrhythmia, sino-atrial pause and to a minor extent supraventricular or ventricular tachycardia, following tamoxifen treatment

atrioventricular block ( J:186021 )

• complete heart block some weeks after tamoxifen treatment

prolonged PR interval ( J:186021 )

• following tamoxifen treatment

• progressive prolongation of the P-R interval tends to result in complete isolated contraction of atria and ventricles with high dose tamoxifen treatment

muscle

abnormal sinoatrial node morphology ( J:186021 )

• ablation of sinoatrial node cells following tamoxifen treatment that varies depending on tamoxifen dose

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
sick sinus syndrome		DOID:13884	OMIM:163800 OMIM:608567	J:186021