Phenotypes for Fxn Tg(Ckmm-cre)5Khn MGI:8472545 MGI Mouse

premature death ( J:345565 )

• death occurs at 18 weeks of age

• however, mice appear normal from birth to 9 weeks of age, with no overt behavioral abnormalities

• by 18 weeks of age, but not at 9 weeks of age, both males and females exhibit increased heart weight-to-body weight ratio and heart-to-tibia length ratio

cardiac hypertrophy ( J:345565 )

• mice develop cardiac hypertrophy by 18 weeks of age

weight loss ( J:345565 )

• males begin to steadily lose weight at 16 weeks of age and females lose weight between 16 and 18 weeks of age, although weight loss is not significant between females at time of necropsy

increased heart weight ( J:345565 )

• by 18 weeks of age, but not at 9 weeks of age, both males and females exhibit increased heart weight-to-body weight ratio and heart-to-tibia length ratio

cardiac hypertrophy ( J:345565 )

• mice develop cardiac hypertrophy by 18 weeks of age

cardiac fibrosis ( J:345565 )

• mice develop cardiac fibrosis at 18 weeks of age, with hearts showing higher pervasive extracelluar collagen deposits around heart fibers

abnormal cardiovascular system physiology ( J:345565 )

• mice develop progressive heart failure, which is more dramatic in males than females

• progressive failure of heart function is not readily apparent until at least 13 weeks of age

• mice show elevated markers (Nppa, Nppb, Gdf15) of cardiac stress over time

decreased cardiac muscle contractility ( J:345565 )

• by 13 weeks of age, ejection fraction is decreased in males and females and continues to decrease at 15 and 18 weeks of age

• at 13 weeks of age, fractional shortening is decreased in males, but not females, but by 15 and 17 weeks of age, both males and females show decreased fractional shortening

• however, no difference is ejection fraction, fractional shortening, or left ventricular mass is seen at 6, 8, and 9 weeks of age

abnormal heart echocardiography feature ( J:345565 )

• mice exhibit decreased ejection fraction and fractional shortening with age, with males showing changes earlier than females

• by 13 weeks of age, males and females show an increase in left ventricular mass which continues to increase at 15 and 17 weeks of age

• males show increased end-systolic volume and diameter by 13 weeks of age, which continues into 15 and 17 weeks, while females show an increase by 15 weeks of age, which continues into 17 weeks of age

• females show reduced end-systolic diameter at 6, 8, and 9 weeks of age, followed by a switch to increased end-systolic diameter at 15 and 17 weeks of age

• males exhibit increased end-diastolic volume by 9 weeks of age, which continues into 13, 15, and 17 weeks of age, while females show increased end-diastolic volume only at 8, 13, and 17 weeks of age

• males exhibit increased end-diastolic diameter at 15 and 17 weeks of age

• females show an initial reduction of end-diastolic diameter at 6, 8, and 9 weeks of age, followed by a switch to increased end-diastolic diameter at 17 weeks of age

• males show no difference in diastolic strain rate at 6, 8, and 9 weeks of age but a reduction by 13 weeks of age which continues at 15 and 17 weeks of age

• females show a reduction in diastolic strain rate at 15 and 17 weeks of age

• mice exhibit increased left ventricular wall thickness, left ventricular posterior wall thickness, and relative wall thickness over time

decreased heart rate ( J:345565 )

• mice show decreased heart rate over time, with males showing a larger decrease than females

cardiomyopathy ( J:345565 )

• mice begin to show progressive cardiomyopathy between 13 and 15 weeks of age, including decreased ejection fraction and fractional shortening, and increased left ventricular mass

• by 18 weeks of age, mice show elevated markers of iron-sulfur (Fe-S) deficiency, cardiac stress, and injury and cardiac fibrosis