Phenotypes for Ppargc1a Ppargc1b MGI:3802666 MGI Mouse

neonatal lethality, incomplete penetrance ( J:137598 )

• 70% of mice die within 24 hours of birth

postnatal lethality, complete penetrance ( J:137598 )

• all mice die prior to day 14

abnormal myocardium layer morphology ( J:137598 )

• mitochondria in heart samples are small and sparse in postnatal ventricular sections compared to in wild-type mice

• after birth, some myocytes are largely or partially devoid of mitochondria, sacomeres and other cellular organelles

• heart cells exhibit a decrease in mitochondrial number and size, abnormal vacuoles and reduced cristae density compared to in wild-type mice

• despite normal myofibrillar volume, cellular mitochondrial and sarcomere volume densities are reduced compared to in wild-type mice

• mitochondria fail to exhibit an increase in mitochondrial density at E17.5 and P0.5 unlike in wild-type mice

• perinatal mitochondrial biogenesis is blocked

abnormal heart development ( J:137598 )

• mice exhibit a general arrest in cardiac maturation

• at P0.5, mice fail to exhibit an increase in cardiac biogenesis observed in wild-type mice

small heart ( J:137598 )

abnormal heart left ventricle morphology ( J:137598 )

• 12 hours after birth, left ventricle diameter is reduced during diastole compared to in wild-type mice

decreased heart left ventricle weight ( J:137598 )

• at 12 hours after birth

abnormal blood circulation ( J:137598 )

• passive and artrial contraction components of diastolic left ventricle filling are uncoupled from systolic left ventricle outflow jet unlike in wild-type mice consistent with intermittent second-degree heart block

• mice exhibit an increase in isovolumic contraction time and isovolumic relaxation time and decreased ejection time compared to wild-type mice

• mice exhibit decreased passive (E) to active (A) ratio and prolonged isovolumic relaxation time consistent with impaired ventricular diastolic relaxation unlike in wild-type mice

decreased cardiac output ( J:137598 )

• despite preservation of left ventricle fractional shortening, cardiac output is reduced compared to in wild-type mice

decreased heart rate ( J:137598 )

• at 12 hours after birth

congestive heart failure ( J:137598 )

abnormal brown adipose tissue morphology ( J:137598 )

• triglyceride content of brown adipose tissue is increased compared to in wild-type mice

• brown adipose tissue mitochondrial and cristae density are less than in wild-type mice

• brown adipocytes exhibit increased lipid droplet size and density compared to in wild-type mice and single homozygotes

abnormal fat cell morphology ( J:137598 )

• brown adipocytes exhibit increased lipid droplet size and density compared to in wild-type mice and single homozygotes

abnormal pulmonary alveolus morphology ( J:137598 )

• postmortem of mice that die within 24 hours of birth reveal alveolar collapse

• however, alveolar morphology is normal prior to death

respiratory distress ( J:137598 )

• at birth, mice exhibit labored breathing

decreased circulating glucose level ( J:137598 )

• modesty lower at birth

decreased triglyceride level ( J:137598 )