Phenotypes Associated with This Genotype

Genotype
MGI:5911349

• Allelic Composition: Tg(Myh6-tTA)6Smbf/0; Tg(tetO-TPR/MET,-EGFP)12Tcre/0
• Genetic Background: FVB.Cg-Tg(Myh6-tTA)6Smbf Tg(tetO-TPR/MET,-EGFP)12Tcre

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

mortality/aging

premature death ( J:241276 )

• mice die at around 4 weeks after birth (between P25 and P27) when doxycycline (DOX) is removed the day following birth to allow activation of MET in postnatal cardiomyocytes

cardiovascular system

pulmonary vascular congestion ( J:241276 )

cardiac hypertrophy ( J:241276 )

• mice show a massive progressive increase in cardiac hypertrophy from P21 to P27 when DOX is removed the day after birth

• hypertrophy is concentric as indicated by increase in the thickness/radius ratio, left ventricle mass, and left mass normalized to body weight

• treating mice with DOX at P21 rescues the cardiac hypertrophy phenotype

abnormal heart echocardiography feature ( J:241276 )

• echocardiography shows reduced left ventricle volumes, in both diastole and systole, in mice when DOX is removed a day after birth

• however, mice do not show systolic dysfunction as assessed by ejection fraction at P27

congestive heart failure ( J:241276 )

• mice die with signs of congestive heart failure including lung edema, alopecia, ascites, dyspnea, cyanosis, and lethargy following the removal of DOX the day after birth

• however, ejection fraction is preserved

behavior/neurological

lethargy ( J:241276 )

• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth

decreased food intake ( J:241276 )

• food intake is normal at P22 but decreases starting from P23 in mice in which DOX was removed the day after birth

growth/size/body

cardiac hypertrophy ( J:241276 )

• mice show a massive progressive increase in cardiac hypertrophy from P21 to P27 when DOX is removed the day after birth

• hypertrophy is concentric as indicated by increase in the thickness/radius ratio, left ventricle mass, and left mass normalized to body weight

• treating mice with DOX at P21 rescues the cardiac hypertrophy phenotype

decreased body weight ( J:241276 )

• greater than 27% decrease in body weight at P27 in mice when DOX is removed the day after birth

• decrease in body weight results from a reduction in body weight gain starting from P20

cachexia ( J:241276 )

• mice in which DOX was removed the day after birth develop a cardiac cachexia syndrome characterized by weight loss and reduced weight gain, decreased food intake, and skeletal muscle wasting

homeostasis/metabolism

cyanosis ( J:241276 )

• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth

pulmonary edema ( J:241276 )

• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth

• mice treated with DOX at P21 show rescue of lung edema

ascites ( J:241276 )

• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth

integument

alopecia ( J:241276 )

• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth

muscle

decreased skeletal muscle weight ( J:241276 )

• mice showing signs of congestive heart failure show wasted hindlimb muscles and have reduced skeletal muscle weight

• treating mice with DOX at P21 rescues the loss of muscular weight

respiratory system

pulmonary vascular congestion ( J:241276 )

pulmonary edema ( J:241276 )

• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth

• mice treated with DOX at P21 show rescue of lung edema

respiratory distress ( J:241276 )

• one of the signs of congestive heart failure that develops in mice when DOX is removed the day after birth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congestive heart failure		DOID:6000		J:241276