Phenotypes associated with this allele

• Allele Symbol: Abcc9^tm1.1Mcn
• Allele Name: targeted mutation 1, Elizabeth M McNally
• Allele ID: MGI:5646147
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Abcc9^tm1.1Mcn/Abcc9^tm1.1Mcn Tg(Tagln-cre)1Her/0	involves: 129 * 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5770475

Genotype
MGI:5770475

cn1

• Allelic Composition: Abcc9^tm1.1Mcn/Abcc9^tm1.1Mcn; Tg(Tagln-cre)1Her/0
• Genetic Background: involves: 129 * 129S1/Sv * 129X1/SvJ * C57BL/6J

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

mortality/aging

postnatal lethality, complete penetrance ( J:216539 )

• mice die within 14 days of birth from cardiomyopathy and heart failure

cardiovascular system

abnormal myocardial fiber mitochondrial morphology ( J:216539 )

• at P8, cardiac mitochondria display an immature pattern with reduced cross-sectional area and intermitochondrial contacts relative to wild-type mitochondria

• however, mitochondrial DNA content is normal

abnormal fetal cardiomyocyte morphology ( J:216539 )

• lipid droplet accumulation in neonatal cardiomyocytes, unlike in wild-type hearts

enlarged heart ( J:216539 )

increased heart weight ( J:216539 )

• increased heart weight to tibia length ratio relative to wild-type controls

decreased cardiac muscle contractility ( J:216539 )

• progressive decrease in ejection fraction from P6 to P11

• M-mode echocardiograms revealed a decline in fractional shortening at P11

• however, no increase of apoptosis in P7 ventricles, as shown by TUNEL assays

abnormal fetal cardiomyocyte physiology ( J:216539 )

• pinacidil (a KATP channel opener) fails to produce a robust current increase in neonatal cardiomyocytes, unlike in wild-type controls

• mitochondria from neonatal cardiomyocytes are unresponsive to the KATP agonist diazoxide, consistent with with reduced or absent mitochondrial KATP activity

• rapid loss of mitochondrial membrane potential in isolated neonatal cardiomyocytes after exposure to hydrogen peroxide, indicating reduced resistance to cell stress relative to wild-type cardiomyocytes

• mitochondria show a reduced oxygen consumption rate, lack pinacidil responsiveness, and fail to increase oxygen consumption after FCCP treatment, unlike wild-type mitochondria

• failure to fuse and form larger mitochondria in neonatal cardiomyocytes from P2 to P8

• reduced fatty acid oxidation in neonatal cardiomyocytes after palmitate application

cardiomyopathy ( J:216539 )

• neonatal cardiomyopathy due to failure of the newborn myocardium to transition normally from fetal to mature (oxidative) metabolism

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:216539 )

N • nonfasting serum glucose levels are normal at P5-P7

decreased fatty acid oxidation ( J:216539 )

• reduced fatty acid oxidation in neonatal cardiomyocytes after palmitate application

decreased oxygen consumption ( J:216539 )

• cardiac mitochondria show a reduced oxygen consumption rate, lack pinacidil responsiveness, and fail to increase oxygen consumption after treatment with FCCP (a mitochondrial uncoupling agent), unlike wild-type mitochondria

hypoxia ( J:216539 )

• neonatal cardiomyocytes appear to be in a hypoxic state due to their inability to transition to fatty acid oxidation

cellular

abnormal myocardial fiber mitochondrial morphology ( J:216539 )

• at P8, cardiac mitochondria display an immature pattern with reduced cross-sectional area and intermitochondrial contacts relative to wild-type mitochondria

• however, mitochondrial DNA content is normal

decreased mitochondrial size ( J:216539 )

• failure to fuse and form larger mitochondria in neonatal cardiomyocytes from P2 to P8

increased cellular sensitivity to hydrogen peroxide ( J:216539 )

• neonatal cardiomyocytes are more susceptible to cell death in response to H2O2-induced stress relative to wild-type controls

• opening of KATP channels with pinacidil is less cardioprotective than in wild-type cardiomyocytes

abnormal mitochondrial physiology ( J:216539 )

• mitochondria from neonatal cardiomyocytes are unresponsive to the KATP agonist diazoxide, consistent with with reduced or absent mitochondrial KATP activity

• rapid loss of mitochondrial membrane potential in isolated neonatal cardiomyocytes following cell stress induced by exposure to hydrogen peroxide, unlike in wild-type cardiomyocytes

• mitochondria show a reduced oxygen consumption rate, lack pinacidil responsiveness, and fail to increase oxygen consumption after treatment with FCCP (a mitochondrial uncoupling agent), unlike wild-type mitochondria

decreased fatty acid oxidation ( J:216539 )

• reduced fatty acid oxidation in neonatal cardiomyocytes after palmitate application

oxidative stress ( J:216539 )

• increased reactive oxygen species in isolated neonatal cardiomyocytes, as shown by increased dihydroethidium staining relative to wild-type controls

muscle

abnormal myocardial fiber mitochondrial morphology ( J:216539 )

• at P8, cardiac mitochondria display an immature pattern with reduced cross-sectional area and intermitochondrial contacts relative to wild-type mitochondria

• however, mitochondrial DNA content is normal

decreased cardiac muscle contractility ( J:216539 )

• however, no increase of apoptosis in P7 ventricles, as shown by TUNEL assays

• progressive decrease in ejection fraction from P6 to P11

• M-mode echocardiograms revealed a decline in fractional shortening at P11

cardiomyopathy ( J:216539 )

• neonatal cardiomyopathy due to failure of the newborn myocardium to transition normally from fetal to mature (oxidative) metabolism

growth/size/body

enlarged heart ( J:216539 )

increased heart weight ( J:216539 )

• increased heart weight to tibia length ratio relative to wild-type controls