cardiovascular system phenotype

• abnormal fetal cardiomyocyte morphology
  • notably at E9.5, numerous mitochondria in the ventricular subepicardial myocytes appear significantly inflated and irregularly shaped, suggesting mitochondrial cardiomyopathy
  (MGI Ref ID J:58223)

• thin interventricular septum
  • at E9.5, homozygotes display severe thinning of the ventricular septum
  (MGI Ref ID J:58223)

• thin ventricular wall
  • at E9.5, homozygotes display severe thinning of the ventricular wall
  (MGI Ref ID J:58223)

• abnormal placental labyrinth vasculature morphology
  • at E9.5, mutant placentas exhibit abnormal fetal and maternal vascular networks, with fetal vessels rarely permeating the presumptive labyrinth
  (MGI Ref ID J:58223)
  • maternal blood sinuses appear frequently dilated, ruptured, and thus adjoined within mutant placentas, often forming a continuous blood pool throughout the entire zone
  (MGI Ref ID J:58223)
  • maternal erythrocytes, normally restricted to the sinuses, are noted throughout the cytoplasms of cells in the mutant junctional zone, indicating obvious erythrophagocytic activity of the trophoblasts lining the maternal sinuses
  (MGI Ref ID J:58223)

• thin ventricle myocardium compact layer
  • at E9.5, homozygotes exhibit severe thinning of the compact zone of the ventricular myocardium
  (MGI Ref ID J:58223)

• abnormal myocardial fiber morphology
  • at E9.5, homozygotes exhibit premature differentiation of ventricular subepicardial myocytes, as shown by frequent tandem sarcomers, separated by multiple Z lines, crossing cell boundaries through intercalated discs
  (MGI Ref ID J:58223)

• abnormal myocardial trabeculae morphology
  • at E9.5, homozygotes display degeneration of the trabecular zone
  (MGI Ref ID J:58223)

• thin myocardium
  (MGI Ref ID J:58223)

embryo phenotype

• abnormal placental labyrinth vasculature morphology
  • maternal blood sinuses appear frequently dilated, ruptured, and thus adjoined within mutant placentas, often forming a continuous blood pool throughout the entire zone
  (MGI Ref ID J:58223)
  • at E9.5, mutant placentas exhibit abnormal fetal and maternal vascular networks, with fetal vessels rarely permeating the presumptive labyrinth
  (MGI Ref ID J:58223)
  • maternal erythrocytes, normally restricted to the sinuses, are noted throughout the cytoplasms of cells in the mutant junctional zone, indicating obvious erythrophagocytic activity of the trophoblasts lining the maternal sinuses
  (MGI Ref ID J:58223)

• abnormal placenta hemotrichorial membrane morphology
  • at E9.5, homozygotes show a dramatic decrease of lipid droplet accumulation in the three cell-layered labyrinthine barrier, with scarce lipid droplets found in presumptive hemotrichorial layers I and II, and miniscule lipid droplets found in layer III
  (MGI Ref ID J:58223)

• abnormal placenta morphology
  (MGI Ref ID J:58223)

• abnormal trophoblast layer morphology
  • at E9.5, homozygotes display failure of fetal vessel permeation, phagocytosis of maternal blood cells, incomplete epithelialization of the labyrinthine barrier, and loose endothelial trophoblast contacts
  (MGI Ref ID J:58223)

• abnormal chorionic plate morphology
  • at E9.5, mutant embryos display abnormal thickening of the chorionic plate, with poorly differentiated chorionic villi and reduced hemotrichorial layer characteristics
  (MGI Ref ID J:58223)

• abnormal placenta labyrinth morphology
  • at E9.5, mutant embryos display a maturation block in labyrinthine trophoblast, with an abnormally thick trophoblast tissue retaining features of the early labyrinthine parenchyma
  (MGI Ref ID J:58223)

• abnormal trophoblast giant cell morphology
  • at E9.5, the mutant trophoblast epithelium is less compact while the fetal endothelium is detached from hemotrichorial layer III
  (MGI Ref ID J:58223)

mortality/aging

• embryonic lethality during organogenesis, complete penetrance
  • however, all mutant embryos obtained after E9.5 are dead and display progressive necrosis
  (MGI Ref ID J:58223)
  • at E9.5 or earlier, homozygous mutant embryos are recovered at the expected Mendelian ratio and appear normal in both size and gross morphology
  (MGI Ref ID J:58223)

muscle phenotype

• abnormal myocardial fiber morphology
  • at E9.5, homozygotes exhibit premature differentiation of ventricular subepicardial myocytes, as shown by frequent tandem sarcomers, separated by multiple Z lines, crossing cell boundaries through intercalated discs
  (MGI Ref ID J:58223)

• thin ventricle myocardium compact layer
  • at E9.5, homozygotes exhibit severe thinning of the compact zone of the ventricular myocardium
  (MGI Ref ID J:58223)

• thin myocardium
  (MGI Ref ID J:58223)

• abnormal myocardial trabeculae morphology
  • at E9.5, homozygotes display degeneration of the trabecular zone
  (MGI Ref ID J:58223)

homeostasis/metabolism phenotype

• abnormal glucose homeostasis
  (MGI Ref ID J:60354)

• increased insulin sensitivity
  • improved insulin sensitivity may be associated with increased serum leptin levels, as heterozygotes do show a significant increase in leptin mRNA expression
  (MGI Ref ID J:60354)
  • unexpectedly, during oral glucose tolerance tests, heterozygotes are able to maintain wild-type glucose levels, despite a significant reduction in plasma insulin concentrations
  (MGI Ref ID J:60354)
  • during glucose clamp experiments, heterozygotes show a 30% increase in the insulin-induced glucose disposal rate relative to wild-type mice
  (MGI Ref ID J:60354)
  • male heterozygotes are apparently healthy and exhibit no significant differences in body weight, fat-pad, basal fasting glucose and insulin levels or FFA levels relative to wild-type mice
  (MGI Ref ID J:60354)
  • similarly, heterozygotes exhibit a significant increase in insulin-induced suppression of hepatic glucose production relative to wild-type mice
  (MGI Ref ID J:60354)