Mouse Genome Informatics
hm
    Lmnatm3Stw/Lmnatm3Stw
involves: 129S1/Sv * 129S4/SvJaeSor * C57BL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• homozygotes generally die between 12 - 14 weeks of age with none surviving past 16 weeks of age
• in at least 3 homozygotes death resulted from bradyarrhythmia

growth/size
• homozygotes display decreased weight gain starting around 4 weeks of age

cardiovascular system
• loss of sarcomere organization is seen in cardiomyocytes and nuclear defects are seen
• degeneration is associated with decreased fiber size, fragmentation, increased granular cytoplasm with loss of striation, and occasional vacuolation
• dilation of the chambers is accompanied by thinning of the chamber walls
• increased cardiac interstitial fibrosis is seen at 9 weeks of age; however, no increase in apoptosis is detected
• increased levels of atrial natriuretic peptide and B-type natriuretic peptide are seen
• progressive decrease in ventricular fractional shortening is seen starting at 8 weeks of age and left ventricular end-diastolic dimension is significantly larger compared to controls when normalized to body weight
• continuous electrocardiographic monitoring revealed periods of extreme bradycardia and excessive diurnal variation in heart rate in 8 week old mutants
• continuous electrocardiographic monitoring revealed a variety of conduction abnormalities including 2 mice with progressive prolongations of the PR interval

behavior/neurological
• just prior to death homozygotes display reduced activity

muscle
• loss of sarcomere organization is seen in cardiomyocytes and nuclear defects are seen
• degeneration is associated with decreased fiber size, fragmentation, increased granular cytoplasm with loss of striation, and occasional vacuolation
• increased levels of atrial natriuretic peptide and B-type natriuretic peptide are seen
• progressive decrease in ventricular fractional shortening is seen starting at 8 weeks of age and left ventricular end-diastolic dimension is significantly larger compared to controls when normalized to body weight
• moderate degeneration of cardiac muscle but only very mild degeneration of skeletal muscle is seen

integument
• just prior to death homozygotes appear slightly disheveled

Mouse Models of Human Disease
OMIM IDRef(s)
Cardiomyopathy, Dilated, 1A; CMD1A 115200 J:100393