Phenotypes Associated with This Genotype

Genotype
MGI:4947241

• Allelic Composition: Jup^tm1.1Glr/Jup^tm1.1Glr; A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/N * SJL

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

mortality/aging

premature death ( J:170618 )

• increase in cardiac death compared to controls beginning about 3 months after tamoxifen treatment

cardiovascular system

cardiovascular system phenotype ( J:170618 )

N • unlike in human patients with Arrhythmogenic Right Ventricular Dysplasia replacement of myocytes with adipocytes is not seen in tamoxifen treated mice and tamoxifen treated mice are not more susceptible to induced arrhythmias

abnormal myocardial fiber morphology ( J:170618 )

• decrease in the number and length of desmosomes in tamoxifen treated mice

• adherens-type junctions with less submembranous electron-dense material are prominently seen in tamoxifen treated mice

abnormal intercalated disk morphology ( J:170618 )

• mislocalization of desmosomal proteins to the intercalated disc in tamoxifen treated mice

increased myocardial fiber size ( J:170618 )

• increase in cardiomyocyte cross sectional area with age in tamoxifen treated mice

increased heart weight ( J:170618 )

• increase in the heart to body weight ratio with age in tamoxifen treated mice

increased heart left ventricle size ( J:170618 )

• by about 5 months after tamoxifen treatment

heart left ventricle hypertrophy ( J:170618 )

• mild left ventricle hypertrophy in tamoxifen treated mice

dilated heart left ventricle ( J:170618 )

• modest left ventricle dilation in tamoxifen treated mice

abnormal heart right ventricle morphology ( J:170618 )

• progressive thinning of the right ventricular free wall is seen after tamoxifen treatment

increased heart right ventricle size ( J:170618 )

• by about 5 months after tamoxifen treatment

cardiac fibrosis ( J:170618 )

• focal areas of myocyte loss and replacement with fibrous tissue are seen after tamoxifen treatment

abnormal cardiovascular system physiology ( J:170618 )

• increased apoptosis is seen at 5 months after tamoxifen treatment

• apoptotic cells are associated with fibrotic areas

• heart failure is seen in some tamoxifen treated mice

decreased heart left ventricle muscle contractility ( J:170618 )

• reduction of left ventricular fractional shortening and ejection fraction in tamoxifen treated mice

heart inflammation ( J:170618 )

• infiltration of activated macrophages/monocytes in areas adjacent to apoptotic myocytes in tamoxifen treated mice

• neutrophil infiltrations are also seen in tamoxifen treated mice

muscle

abnormal myocardial fiber morphology ( J:170618 )

• decrease in the number and length of desmosomes in tamoxifen treated mice

• adherens-type junctions with less submembranous electron-dense material are prominently seen in tamoxifen treated mice

abnormal intercalated disk morphology ( J:170618 )

• mislocalization of desmosomal proteins to the intercalated disc in tamoxifen treated mice

increased myocardial fiber size ( J:170618 )

• increase in cardiomyocyte cross sectional area with age in tamoxifen treated mice

heart left ventricle hypertrophy ( J:170618 )

• mild left ventricle hypertrophy in tamoxifen treated mice

decreased heart left ventricle muscle contractility ( J:170618 )

• reduction of left ventricular fractional shortening and ejection fraction in tamoxifen treated mice

abnormal sarcomere morphology ( J:170618 )

• cardiomyocyte sarcomeres appear distorted and compressed in tamoxifen treated mice

• decreased cardiomyocyte sarcomere length in tamoxifen treated mice

diffuse Z line ( J:170618 )

• cardiomyocyte sarcomeres have wider, less dense Z lines in tamoxifen treated mice

homeostasis/metabolism

pulmonary edema ( J:170618 )

• seen at 9 - 12 months after tamoxifen treatment, associated with heart failure

abnormal interleukin level ( J:170618 )

• increase in the IL6 and IL1B levels in heart lysates from tamoxifen treated mice

• increase in cytokine expression is associated with the severity of myocyte loss

immune system

heart inflammation ( J:170618 )

• infiltration of activated macrophages/monocytes in areas adjacent to apoptotic myocytes in tamoxifen treated mice

• neutrophil infiltrations are also seen in tamoxifen treated mice

abnormal interleukin level ( J:170618 )

• increase in the IL6 and IL1B levels in heart lysates from tamoxifen treated mice

• increase in cytokine expression is associated with the severity of myocyte loss

respiratory system

pulmonary edema ( J:170618 )

• seen at 9 - 12 months after tamoxifen treatment, associated with heart failure

growth/size/body

heart left ventricle hypertrophy ( J:170618 )

• mild left ventricle hypertrophy in tamoxifen treated mice

increased heart weight ( J:170618 )

• increase in the heart to body weight ratio with age in tamoxifen treated mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
arrhythmogenic right ventricular dysplasia 12		DOID:0110083	OMIM:611528	J:170618