Phenotypes Associated with This Genotype

Genotype
MGI:3589459

• Allelic Composition: Lmna^tm3Stw/Lmna^tm3Stw
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * C57BL

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

mortality/aging

premature death ( J:100393 )

• 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/body

postnatal growth retardation ( J:100393 )

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

cardiovascular system

abnormal myocardial fiber morphology ( J:100393 )

• loss of sarcomere organization is seen in cardiomyocytes and nuclear defects are seen

myocardial fiber degeneration ( J:100393 )

• degeneration is associated with decreased fiber size, fragmentation, increased granular cytoplasm with loss of striation, and occasional vacuolation

thin myocardium ( J:100393 )

• dilation of the chambers is accompanied by thinning of the chamber walls

cardiac muscle degeneration ( J:100393 )

• moderate degeneration of cardiac muscle but only very mild degeneration of skeletal muscle is seen

cardiac interstitial fibrosis ( J:100393 )

• increased cardiac interstitial fibrosis is seen at 9 weeks of age; however, no increase in apoptosis is detected

dilated cardiomyopathy ( J:100393 )

• increased levels of atrial natriuretic peptide and B-type natriuretic peptide are seen

decreased ventricle muscle contractility ( J:100393 )

• 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

decreased heart rate ( J:100393 )

• continuous electrocardiographic monitoring revealed periods of extreme bradycardia and excessive diurnal variation in heart rate in 8 week old mutants

prolonged PR interval ( J:100393 )

• continuous electrocardiographic monitoring revealed a variety of conduction abnormalities including 2 mice with progressive prolongations of the PR interval

behavior/neurological

decreased locomotor activity ( J:100393 )

• just prior to death homozygotes display reduced activity

muscle

abnormal myocardial fiber morphology ( J:100393 )

• loss of sarcomere organization is seen in cardiomyocytes and nuclear defects are seen

myocardial fiber degeneration ( J:100393 )

• degeneration is associated with decreased fiber size, fragmentation, increased granular cytoplasm with loss of striation, and occasional vacuolation

thin myocardium ( J:100393 )

• dilation of the chambers is accompanied by thinning of the chamber walls

cardiac muscle degeneration ( J:100393 )

• moderate degeneration of cardiac muscle but only very mild degeneration of skeletal muscle is seen

dilated cardiomyopathy ( J:100393 )

• increased levels of atrial natriuretic peptide and B-type natriuretic peptide are seen

decreased ventricle muscle contractility ( J:100393 )

• 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

integument

disheveled coat ( J:100393 )

• just prior to death homozygotes appear slightly disheveled

cellular

cardiac interstitial fibrosis ( J:100393 )

• increased cardiac interstitial fibrosis is seen at 9 weeks of age; however, no increase in apoptosis is detected

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy 1A		DOID:0110425	OMIM:115200	J:100393