Phenotypes for Lmna MGI:5906504 MGI Mouse

premature death ( J:198526 )

• mice die between 35 and 70 weeks of age

• death occurs about 15-20 weeks after reduced fractional shortening

cardiac muscle degeneration ( J:198526 )

• at end stage, degenerative changes are seen in cardiac tissues with disrupted sarcomeres, myofibrillar lysis, vesicular proliferation of sarcomeric reticulum, intracytoplasmic junctions, electron dense residual bodies, and pericellular fibrosis

abnormal heart morphology ( J:198526 )

• large proportion of nuclei in the heart are more elongated and thinner at 10, 30, and 57 weeks of age and these nuclei have enlarged nuclear intermembrane space in young asymptomatic mice

• mice with mild cardiac dysfunction show severe alterations in cardiac nuclei, such as extremely enlarged nuclear intermembrane space, accumulation of large perinuclear vacuoles, or envelope rupture with extravasations of chromatin into the cytoplasm

increased heart atrium size ( J:198526 )

• atrial enlargement

cardiac hypertrophy ( J:198526 )

dilated heart left ventricle ( J:198526 )

• increase in left ventricular end-diastolic diameter

• however, no major wall thinning is seen

cardiac fibrosis ( J:198526 )

• at end stage, the left ventricle shows slight fibrosis

dilated cardiomyopathy ( J:198526 )

• mice exhibit decreased fractional shortening and increased left ventricle end-diastolic diameter indicating dilated cardiomyopathy

decreased cardiac muscle contractility ( J:198526 )

• progressive development of cardiac dysfunction from 32 to 70 weeks of age

• decrease in fractional shortening which starts a bit earlier in males than in females

abnormal heart echocardiography feature ( J:198526 )

• echocardiography indicates decreased fractional shortening and increased left ventricle end-diastolic diameter without wall thinning

decreased heart rate ( J:198526 )

• slight bradycardia is seen at the very end stages of the dilated cardiomyopathy

prolonged PR interval ( J:198526 )

• higher PR interval is seen at the very end stages of the dilated cardiomyopathy

prolonged QRS complex duration ( J:198526 )

• QRS complex broadening is seen at the very end stages of the dilated cardiomyopathy

congestive heart failure ( J:198526 )

• mice eventually present with congestive heart failure demonstrated by left ventricle hypokinesia and lung edema

homeostasis/metabolism phenotype ( J:198526 )

N	• 57 week old mice do not exhibit metabolic defects

pulmonary edema ( J:198526 )

• lung edema in mice with congestive heart failure

muscle phenotype ( J:198526 )

N	• 57 week old mice do not exhibit skeletal muscle defects or skeletal muscle contractile function defects