Analysis Tools
mortality/aging
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• homozygotes are present at a normal Mendelian frequency at E18.5 but die soon after birth
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nervous system
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• some homozygotes display a severely abnormal forebrain development
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• at E14.5, the normal thick to thin transition of neuroepithelium marking the mid/hindbrain junction is found caudal to its normal location, suggesting that the mutant posterior midbrain may extend caudally
• in addition, the mutant posterior midbrain exhibits aberrant A-P patterning
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• at E12.5, normal derivatives of the isthmus (isthmic nuclei; IV motor nucleus) and r1-3 (cerebellum, locus coeruleus, V motor nucleus) fail to develop
• however, no defects in brain or spinal cord derivatives of regions posterior to r3 are noted from E12.5 through P0
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• at E14.5-E16.5, the junction between the midbrain and developing cerebellum (isthmus) is more caudally positioned than normal
• at E9.5-E10.5, the neuroepithelium at the mid/hindbrain junction is abnormal on its posterior side
• by E9.5, the region between the posterior end of the midbrain and r4 (i.e. anterior hindbrain) is severely reduced in length
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• at E14.5-E16.5, the developing choroid plexus appears to be fused to the amorphous tissue found in place of a normal cerebellum
• by E17.5-P0, the mutant choroid plexus is abnormally small and structurally underdeveloped
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• at E14.5, the inferior colliculus of the dorsal midbrain appears as a thickened, extended tissue that resembles the superior colliculus
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• at E9.5-E10.5, the anterior hindbrain is significantly reduced along the A-P axis and its ventral wall is morphologically abnormal
• at E9.5-E10.5, the neuroepithelium at the mid/hindbrain junction is abnormal on its posterior side
• anterior hindbrain defects can be traced back to an early stage of neuraxis development (at least E8.5) and are noted as early as E7.75
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• at E9.5-E10.5, the anterior hindbrain is significantly reduced along the A-P axis and its ventral wall is morphologically abnormal
• anterior hindbrain defects can be traced back to an early stage of neuraxis development (at least E8.5) and are noted as early as E7.75
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• at E12.5-E13.5, the region caudal to the midbrain that includes the cerebellar anlage is reduced in A-P length and appears disorganized
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• at E17.5-P0, the wall of the rostral pontine region is unusually thin, with abnormal architecture
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• at E14.5-E16.5, the locus coeruleus, which is derived from r1, is absent
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• at E14.5-E16.5, all homozygotes exhibit a reduced and morphologically abnormal structure in place of a developing cerebellum
• by E17.5-P0, homozygotes display a small amorphous tissue of variable size and morphology instead of a normal cerebellum in the anterior hindbrain
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• at E14.5-E16.5, the IV motor nucleus and V motor nucleus, which are derived from the isthmus and r2/r3, respectively, are absent
• in contrast, the III motor nucleus in the midbrain, and the VII motor nucleus, which forms in r4/r5 and then migrates to r6 are present and appear normal
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hearing/vestibular/ear
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• at E9.5-E10.5, mutant otocysts are smaller and laterally displaced, in abnormal proximity to the midbrain
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• some mutant embryos exhibit abnormal development of the dorsal membranous labyrinth
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craniofacial
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• some mutant embryos show a significantly reduced or absent supraoccipital bone
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skeleton
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• some mutant embryos show a significantly reduced or absent supraoccipital bone
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