growth/size/body region phenotype

• facial cleft
  • at E12.5, mutant nasal prominencesare not completely merged with each other and to the maxillary prominences
  (MGI Ref ID J:70060)

hematopoietic system phenotype

• anemia
  • at E14.5, all homozygous mutant embryos lack circulating red blood cells
  (MGI Ref ID J:70060)

integument phenotype

• pallor
  • at E14.5, all homozygous mutant embryos are pale
  (MGI Ref ID J:70060)

mortality/aging

• lethality throughout fetal growth and development, complete penetrance
  • homozygous mutant embryos die by E14.5
  (MGI Ref ID J:70060)

nervous system phenotype

• abnormal hindbrain morphology
  • at E9.5, the hindbrain neuroepithelium is not fused and the hindbrain appears morphologically abnormal
  (MGI Ref ID J:70060)

• abnormal dorsal root ganglion morphology
  • at E12.5 and E13.5, mutant dorsal root ganglia are irregular in size and shape, and are sometimes not segmented
  (MGI Ref ID J:70060)
  • Normal - however, no obvious somite patterning defect is detected
  (MGI Ref ID J:70060)

• abnormal neural tube morphology
  • at E10.5, ~63% of homozygous mutant embryos show NTDs
  (MGI Ref ID J:70060)
  • starting at E9.5, homozygotes display neural tube defects (NTDs), with both the anterior midbrain and the hindbrain being open
  (MGI Ref ID J:70060)

• abnormal hindbrain development
  • at E9.5, the mutant hindbrain fails to elevate and forms a convex configuration instead of the V-shaped neural tube observed in wild-type embryos
  (MGI Ref ID J:70060)

• abnormal midbrain morphology
  • at E9.5, the rostral midbrain appears morphologically abnormal
  (MGI Ref ID J:70060)

• intracranial hemorrhage
  • at E10.5, homozygous mutant embryos show hemorrhage into the telencephalic vesicles
  (MGI Ref ID J:70060)

• exencephaly
  • at E12.5, 77% of homozygous mutant embryos display exencephaly resulting from NTDs, while the remaining embryos dot not exhibit NTDs
  (MGI Ref ID J:70060)

• increased embryonic neuroepithelium apoptosis
  • at E8.5 and E9.5, homozygous mutant embryos show a 7-fold increase in apoptotic cell death in the ventral half of the neuroepithelium of the hindbrain, as shown by TUNEL assays
  (MGI Ref ID J:70060)

• spina bifida
  • at E12.5 and E13.5, 37% of homozygous mutant embryos display spina bifida in the posterior neuropore (caudal zone)
  (MGI Ref ID J:70060)

• open neural tube
  • at E9.5, homozygous mutant embryos display an open and everted neural tube
  (MGI Ref ID J:70060)

• abnormal neuron specification
  • at E9.5 and E10.5, the number of betaIII-tubulin positive cells is significantly reduced in the hindbrain of mutant embryos
  (MGI Ref ID J:70060)

skeleton phenotype

• abnormal vertebrae morphology
  • at E12.5 and E13.5, mutant vertebrae display a disorganized structure
  (MGI Ref ID J:70060)

cardiovascular system phenotype

• intracranial hemorrhage
  • at E10.5, homozygous mutant embryos show hemorrhage into the telencephalic vesicles
  (MGI Ref ID J:70060)

• internal hemorrhage
  • at E10.5 to E13.5, homozygous mutant embryos display hemorrhagic sites in the brain and along the caudal neural tube
  (MGI Ref ID J:70060)
  • Normal - however, vascular formation remains unaffected at E10.5
  (MGI Ref ID J:70060)

cellular phenotype

• increased apoptosis
  • at E8.5 and E9.5, homozygous mutant embryos show a 7-fold increase in apoptotic cell death in the ventral half of the neuroepithelium of the hindbrain and in the caudal neural tube, as shown by TUNEL assays
  (MGI Ref ID J:70060)

• increased embryonic neuroepithelium apoptosis
  • at E8.5 and E9.5, homozygous mutant embryos show a 7-fold increase in apoptotic cell death in the ventral half of the neuroepithelium of the hindbrain, as shown by TUNEL assays
  (MGI Ref ID J:70060)

craniofacial phenotype

• abnormal craniofacial development
  • at E11.5-E12.5, all homozygous mutant embryos show abnormal craniofacial development, partly due to increased cell death in the neuroepithelium of the hindbrain
  (MGI Ref ID J:70060)

• facial cleft
  • at E12.5, mutant nasal prominencesare not completely merged with each other and to the maxillary prominences
  (MGI Ref ID J:70060)

embryo phenotype

• abnormal neural tube morphology
  • at E10.5, ~63% of homozygous mutant embryos show NTDs
  (MGI Ref ID J:70060)
  • starting at E9.5, homozygotes display neural tube defects (NTDs), with both the anterior midbrain and the hindbrain being open
  (MGI Ref ID J:70060)

• open neural tube
  • at E9.5, homozygous mutant embryos display an open and everted neural tube
  (MGI Ref ID J:70060)

• spina bifida
  • at E12.5 and E13.5, 37% of homozygous mutant embryos display spina bifida in the posterior neuropore (caudal zone)
  (MGI Ref ID J:70060)

cardiovascular system phenotype

• hemorrhage
  • some heterozygous mutant embryos display sites of hemorrhage at E12.5 and blood loss at E14.5
  (MGI Ref ID J:70060)

nervous system phenotype

• forebrain hypoplasia
  (MGI Ref ID J:70060)

• abnormal forebrain morphology
  • at E10.5, affected heterozygotes exhibit an underdeveloped and disorganized forebrain
  (MGI Ref ID J:70060)

• abnormal midbrain morphology
  • at E10.5, affected heterozygotes exhibit an underdeveloped and disorganized midbrain
  (MGI Ref ID J:70060)

• open neural tube
  • at E10.5, a few heterozygotes exhibit an open neural tube
  (MGI Ref ID J:70060)

• abnormal brain morphology
  • at E10.5, 18% of heterozygous mutant embryos display an abnormal brain phenotype that is less severe than that observed in homozygous mutant embryos
  (MGI Ref ID J:70060)

• abnormal hindbrain morphology
  • at E10.5, affected heterozygotes exhibit an underdeveloped and disorganized hindbrain with a collapsed roof
  (MGI Ref ID J:70060)

• abnormal brain development
  • at E10.5, the majority of affected heterozygous mutant embryos display abnormal fore-, mid- and hindbrain development
  (MGI Ref ID J:70060)

• increased embryonic neuroepithelium apoptosis
  • at E10.5, affected heterozygous mutant embryos display excessive apoptosis of neuroepithelial cells in the hindbrain region
  (MGI Ref ID J:70060)

cellular phenotype

• increased embryonic neuroepithelium apoptosis
  • at E10.5, affected heterozygous mutant embryos display excessive apoptosis of neuroepithelial cells in the hindbrain region
  (MGI Ref ID J:70060)

embryo phenotype

• open neural tube
  • at E10.5, a few heterozygotes exhibit an open neural tube
  (MGI Ref ID J:70060)

mortality/aging

• embryonic lethality, incomplete penetrance
  • affected heterozygous mutant embryos exhibit embryonic lethality with excessive neuroepithelial apoptosis in the hindbrain
  (MGI Ref ID J:70060)
  • Normal - however, no overt abnormalities are detected in live-born heterozygous mutant mice
  (MGI Ref ID J:70060)