Mouse Genome Informatics
cn
    Juptm1.1Glr/Juptm1.1Glr
Tg(Myh6-cre/Esr1*)1Jmk/0

involves: 129S6/SvEvTac * C57BL/6 * FVB/N * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• increase in cardiac death compared to controls beginning about 3 months after tamoxifen treatment

cardiovascular system
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 (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
• mislocalization of desmosomal proteins to the intercalated disc in tamoxifen treated mice
• increase in cardiomyocyte cross sectional area with age in tamoxifen treated mice
• increase in the heart to body weight ratio with age in tamoxifen treated mice
• by about 5 months after tamoxifen treatment
• mild left ventricle hypertrophy in tamoxifen treated mice
• modest left ventricle dilation in tamoxifen treated mice
• progressive thinning of the right ventricular free wall is seen after tamoxifen treatment
• by about 5 months after tamoxifen treatment
• focal areas of myocyte loss and replacement with fibrous tissue are seen after tamoxifen treatment
• 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
• reduction of left ventricular fractional shortening and ejection fraction in tamoxifen treated mice
• 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
• 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
• mislocalization of desmosomal proteins to the intercalated disc in tamoxifen treated mice
• increase in cardiomyocyte cross sectional area with age in tamoxifen treated mice
• reduction of left ventricular fractional shortening and ejection fraction in tamoxifen treated mice
• cardiomyocyte sarcomeres have wider, less dense Z lines in tamoxifen treated mice
• cardiomyocyte sarcomeres appear distorted and compressed in tamoxifen treated mice
• decreased cardiomyocyte sarcomere length in tamoxifen treated mice

homeostasis/metabolism
• focal areas of myocyte loss and replacement with fibrous tissue are seen after tamoxifen treatment
• seen at 9 - 12 months after tamoxifen treatment, associated with heart failure
• 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
• infiltration of activated macrophages/monocytes in areas adjacent to apoptotic myocytes in tamoxifen treated mice
• neutrophil infiltrations are also seen in tamoxifen treated mice
• 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
• seen at 9 - 12 months after tamoxifen treatment, associated with heart failure

Mouse Models of Human Disease
OMIM IDRef(s)
Arrhythmogenic Right Ventricular Dysplasia, Familial, 12; ARVD12 611528 J:170618