cardiovascular system phenotype

• intracranial hemorrhage
  • intracranial hemorrhage with varying degrees of severity and time of onset that can appear as early as E12.5
  (MGI Ref ID J:40365)

limbs/digits/tail phenotype

• abnormal hindlimb morphology
  • hindlimbs are curved toward the midline
  (MGI Ref ID J:40365)

• short tail
  (MGI Ref ID J:40365)

• kinked tail
  • by E12.5, all mutants display a kinked tail
  (MGI Ref ID J:40365)

• curly tail
  • tails are curled toward the right side of the body
  (MGI Ref ID J:40365)

mortality/aging

• neonatal lethality, complete penetrance
  • none survive for longer than 30 min after natural birth or C-section
  (MGI Ref ID J:40365)

cellular phenotype

• abnormal neuron differentiation
  (MGI Ref ID J:40365)

nervous system phenotype

• abnormal neuron differentiation
  (MGI Ref ID J:40365)

• abnormal third ventricle morphology
  • the ventricular zone along the mid-portions of the third ventricle is absent in E14.5 mutants
  (MGI Ref ID J:40365)

• dilated lateral ventricles
  (MGI Ref ID J:40365)

• abnormal lateral ganglionic eminence morphology
  • the lateral ganglionic eminence is much less prominent starting at E12.5 than in controls
  (MGI Ref ID J:40365)
  • fewer dividing progenitor cells in the luminal layer of the ventricular zone in the lateral ganglionic eminence, resulting in a thinner ventricular zone
  (MGI Ref ID J:40365)

• abnormal temporal lobe morphology
  • atrophy in the subcortical region of the temporal lobe along the external capsule in the brain
  (MGI Ref ID J:40365)

• neuron degeneration
  • exhibit a progression of neuronal loss from anterior to posterior portions of the cerebral hemispheres
  (MGI Ref ID J:40365)
  • region-specific (the ventricular and subventricular zones in the ventrolateral region of the brain and subcortical region of the temporal lobe) symmetric loss of neurons and neural progenitor cells with varying severity at E17.5-18.5 and in neonates
  (MGI Ref ID J:40365)

• abnormal hippocampus development
  • hippocampal formation is hardly recognizable at E14.5, whereas in controls it is quite prominent
  (MGI Ref ID J:40365)

• abnormal brain morphology
  • the brain shows symmetric cavitation in the ventrolateral region of the ventricular zone in the posterior portion of the brain at E17.5
  (MGI Ref ID J:40365)

• decreased neuronal precursor cell number
  • the ventricular and subventricular zones in the ventrolateral region show severe loss of neural progenitor cells leading to symmetric cavitation at E17.5
  (MGI Ref ID J:40365)

• intracranial hemorrhage
  • intracranial hemorrhage with varying degrees of severity and time of onset that can appear as early as E12.5
  (MGI Ref ID J:40365)

• small embryonic telencephalon
  • smaller at E9.5
  (MGI Ref ID J:40365)

• thin cortical plate
  (MGI Ref ID J:40365)

• abnormal cerebral cortex morphology
  • at the level of the interventricular foramen of Monroe, where the lateral ventricles join the third ventricle, a disruption of the cerebral architecture is seen at E16.5
  (MGI Ref ID J:40365)

• abnormal dentate gyrus morphology
  • dentate gyrus is less distinct than in controls at E17.5
  (MGI Ref ID J:40365)

• abnormal diencephalon morphology
  • the ependymal layer and the ventricular zone at the diencephalic sulcus are disrupted
  (MGI Ref ID J:40365)

craniofacial phenotype

• occipital bone hypoplasia
  • occipital bones are underdeveloped
  (MGI Ref ID J:40365)

respiratory system phenotype

• abnormal pulmonary alveolus morphology
  • the alveoli are poorly expanded, probably due to mechanical difficulties imposed by the malformed ribcage
  (MGI Ref ID J:40365)

skeleton phenotype

• abnormal rib morphology
  • the posterior rib segments are missing and the existing ribs are underossified and fused
  (MGI Ref ID J:40365)

• sacral vertebral fusion
  (MGI Ref ID J:40365)

• abnormal bone ossification
  • axial skeleton has about 12 pairs of underossified bones and 3-4 pairs or random ossification centers followed by an unossified and unsegmented cartilaginous mass on the dorsal aspect of the vertebral column
  (MGI Ref ID J:40365)

• abnormal spine curvature
  • lack the normal cervical and lumbar flexures of the vertebral column
  (MGI Ref ID J:40365)

• lumbar vertebral fusion
  (MGI Ref ID J:40365)

• rib fusion
  • existing ribs are fused
  (MGI Ref ID J:40365)

• abnormal axial skeleton morphology
  • axial skeleton is severely malformed
  (MGI Ref ID J:40365)
  • caudal to the pelvis, the axial skeletal structure is completely missing
  (MGI Ref ID J:40365)

• abnormal costovertebral joint morphology
  • the ribs are detached from the vertebral column and are only present in the thoracic region in association with the underossified bones in the vertebral column
  (MGI Ref ID J:40365)

• decreased rib number
  • homozygotes have only 9-11 instead of 13 pairs of ribs
  (MGI Ref ID J:40365)

• abnormal sternum morphology
  • sternum is shorter, thicker and lacks intersternebral cartilage
  (MGI Ref ID J:40365)

• short sternum
  (MGI Ref ID J:40365)

• vertebral fusion
  (MGI Ref ID J:40365)

• cervical vertebral fusion
  (MGI Ref ID J:40365)

• occipital bone hypoplasia
  • occipital bones are underdeveloped
  (MGI Ref ID J:40365)

embryo phenotype

• short rostral-caudal axis
  • shorter rostro-caudal body axes
  (MGI Ref ID J:40365)

• abnormal rostral-caudal patterning of the somites
  • the segmentation in the caudal region of the somites appears less distinct at E9.5-10.5
  (MGI Ref ID J:40365)

growth/size/body region phenotype

• decreased body length
  (MGI Ref ID J:40365)

• decreased body weight
  • neonates weigh 15-20% less than control littermates
  (MGI Ref ID J:40365)

• abnormal postnatal growth/weight/body size
  • thick neck
  (MGI Ref ID J:40365)

integument phenotype

• loose skin
  (MGI Ref ID J:40365)

cellular phenotype

• abnormal apoptosis
  • at E10 the total number of apoptotic cells and relative percentage of apoptotic cells to progenitor cells in the forebrain-midbrain junction is reduced about 50% compared to littermate controls
  (MGI Ref ID J:90392)