Analysis Tools
mortality/aging
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• all mice die by P30
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• although mice are born at near-Mendelian ratios, only 13% versus expected 25% are obtained at P10
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growth/size/body
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• mice exhibit reduced body weight starting at P14
• at P15-P25, internal organs are smaller in size but grossly normal
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weight loss
(
J:210236
)
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• mice exhibit weight loss after P14
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behavior/neurological
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• at 3 weeks of age, mice display clasping of the hindlimbs when lifted by the tail
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• at 3 weeks of age, mice are unable to walk on a balance beam
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• at P20, mice display frequent missteps when placed on a grid
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• at P20, mice walk with an abnormal wide-based gait of both fore- and hindpaws
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nervous system
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• at P5-P15, granule cells accumulate throughout the molecular layer, rather than migrating and forming the interior granule cell layer as in wild-type controls
• no granule cells with a polarized radially oriented elongated shape typical of migration are present in the molecular layer, unlike in wild-type controls, indicating that inward radial granule cell migration is severely impaired
• however, the morphology and structure of Bergmann glial cells are largely normal
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hydrocephaly
(
J:210236
)
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• all mice develop an enlarged dome-shaped skull, indicating severe progressive hydrocephalus
• however, E19 and newborn mice are grossly normal
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• at P5, the aqueduct diameter is reduced and a clear lumen is absent, indicating aqueductal stenosis
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• at P20, mice show loss of ependymal cells surrounding the ventricles
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• mice show progressive expansion of the lateral ventricles
• enormous expansion of caudal lateral ventricles at P10
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• at P20, mice show loss of white matter surrounding the ventricles
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• at P20, mice show atrophy of the striatum
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• mice exhibit disrupted laminar organization in the hippocampus
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• at P10, the hippocampus pyramidal layer appears disorganized
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• at P20, mice show atrophy of the hippocampus
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• mice exhibit disrupted laminar organization in the cortex
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• at P20, mice show severe thinning of the cortex
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• at P20, mice show atrophy of the lateral septum
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• at P20, mice show atrophy of several telencephalic areas, including the striatum, lateral septum, and hippocampus
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• mice exhibit disrupted laminar organization in the cerebellar cortex, indicating absence of radial granule cell migration
• at P16, cell bodies of Purkinje cells are abnormally positioned near the white matter, while other neurons are spread over a single superficial layer containing both molecular layer interneurons as well as a high density of granule cells
• however, folial organization of the vermis is intact at P11, and cerebellar cortex appears normal at P2 (before the onset of radial migration)
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• at P16, cell bodies of Purkinje cells are abnormally positioned near the white matter
• occasionally, glomeruli-like structures occur near the Purkinje cell layer
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• at P16, Purkinje cell dendritic arbors extend up to the pial surface
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• cerebellar Golgi cells, which are normally localized in the granule cell layer, are abnormally found between the white matter and the Purkinje cell layer, and do not occur in the single molecular/granule cell layer
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• at P16, the internal granule cell layer is absent
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• at P16, a high density of granule cells is abnormally found in the molecular layer
• at P7-P15, tenascin C levels, normally abundant in the wild-type molecular layer, are abnormally low throughout the cerebellar cortex, indicating altered extracellular matrix composition
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• at P10, the cerebellum is disproportionally smaller than normal
• however, subdivision in vermis and hemispheres and foliation are largely intact
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craniofacial
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• at P20, mice exhibit a dome-shaped skull
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cellular
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• at P5-P15, granule cells accumulate throughout the molecular layer, rather than migrating and forming the interior granule cell layer as in wild-type controls
• no granule cells with a polarized radially oriented elongated shape typical of migration are present in the molecular layer, unlike in wild-type controls, indicating that inward radial granule cell migration is severely impaired
• however, the morphology and structure of Bergmann glial cells are largely normal
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• at P15, mice exhibit altered extracellular matrix composition with significantly lower levels of tenascin C (a protein produced by Bergmann glia cells) throughout the cerebellar cortex
• no doublecortin (DCX, an early neuronal migration and differentiation marker) is detected in cerebellum extracts
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skeleton
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• at P20, mice exhibit a dome-shaped skull
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