Analysis Tools
mortality/aging
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• homozygotes die perinatally for unknown reasons
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nervous system
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• increase in the number of Pax6+ radial glia at the neocortical ventricular zone (VZ) at E12.5 and E14.5
• however, density of Pax6+ cells is not altered within the VZ
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• a 24 h EdU pulse-chase assay showed a ~25% reduction in total neuronal output (EdU+/Ki67- cells basal to the SVZ) per hemisphere along with a ~20% increase in the quit-fraction of cells that have exited the cell cycle, suggesting a more rapid turnover of intermediate progenitors into neurons
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• analysis of cortical layer-specific markers Tbr1 (layer VI) and Ctip2 (layer V) at P0 revealed that heterotopic clusters of cells migrate to superficial laminar positions forming focal cortical dysplasia within the somatosensory area of the neocortex
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• increase in the proliferation of Pax6+ radial glia at the neocortical VZ at E12.5 and E14.5, likely at the expense of differentiative mitoses that produce intermediate progenitors
• significant reduction in the % of phosphohistone H3+ (pHH3+) mitotic cells that are also Wdfy3+ within the VZ at E12.5 and E14.5
• however, no changes in apoptosis are observed in the cerebral cortex at E15.5, as shown by TUNEL analysis
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• as early as E11.5, forebrain shows overt neurodevelopmental anomalies affecting the ganglionic eminences
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• thinning of the intermediate zone at E15.5
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• thinning of the ventricular zone (VZ) at E15.5
• thinning of the Pax6+ VZ at E14.5 at the most lateral positions
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• loss of the subplate by E18.5
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• enlarged lateral ventricles at E11.5 and E18.5
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• enlarged third ventricle at E11.5
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• enlargement of the most frontal aspects of the cerebral cortex at E18.5
• enlargement of the frontopolar cortex with cortical thinning at anterior aspects
• cerebral cortex lamination defects at E18.5
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• radial thinning of the neocortex in basolateral aspects at E15.5
• tangential expansion but lateral thinning of the neocortical neuroepithelium
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• 62% increase in neocortical length at E15.5, with total neocortical area enlarged by ~30%
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• heterotopic clusters of cells migrate to superficial laminar positions forming focal cortical dysplasia within the somatosensory area of the neocortex
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• analysis of cortical lamination markers Tbr1 (layer VI) and Ctip2 (layer V) revealed abnormal layer formation within the somatosensory cortex at P0
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• cortical thinning at anterior aspects at E18.5
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• significant reduction in the size of olfactory bulbs at E18.5
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• thinning of the subventricular zone (SVZ) at E15.5
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• reduced lateral ganglionic eminences with a less rounded outline at E11.5
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• reduced medial ganglionic eminences with a less rounded outline at E11.5
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• ~30% reduction in the Tbr2+ area encompassing the VZ and SVZ, with a ~50% reduction in the density of Tbr2+ intermediate progenitor cells at E15.5
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• heterotopic clusters of cells migrate to superficial laminar positions forming focal cortical dysplasia within the somatosensory area of the neocortex
• most heterotopia consist of only a few dozen cells with limited radial dispersion suggesting a possible origin from Wdfy3+ clusters undergoing pathological changes
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cellular
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• at E12.5 and E15.5, brains do not exhibit any overt signs of macroautophagic flux deregulation, as measured by levels of P62 and LC3II expression as well as accrual of ubiquitinated proteins
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• at E13.5, S-phase length is decreased to 2.5 h relative to ~3.6 h in wild-type cortical segments
• total cell cycle length is decreased to 6.8 h from ~9.8 h in wild-type controls, confirming a more rapid mode of cortical progenitor divisions
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• increase in the number of Pax6+ radial glia at the neocortical ventricular zone (VZ) at E12.5 and E14.5
• however, density of Pax6+ cells is not altered within the VZ
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• a 24 h EdU pulse-chase assay showed a ~25% reduction in total neuronal output (EdU+/Ki67- cells basal to the SVZ) per hemisphere along with a ~20% increase in the quit-fraction of cells that have exited the cell cycle, suggesting a more rapid turnover of intermediate progenitors into neurons
|
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• analysis of cortical layer-specific markers Tbr1 (layer VI) and Ctip2 (layer V) at P0 revealed that heterotopic clusters of cells migrate to superficial laminar positions forming focal cortical dysplasia within the somatosensory area of the neocortex
|
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• increase in the proliferation of Pax6+ radial glia at the neocortical VZ at E12.5 and E14.5, likely at the expense of differentiative mitoses that produce intermediate progenitors
• significant reduction in the % of phosphohistone H3+ (pHH3+) mitotic cells that are also Wdfy3+ within the VZ at E12.5 and E14.5
• however, no changes in apoptosis are observed in the cerebral cortex at E15.5, as shown by TUNEL analysis
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| autism spectrum disorder | DOID:0060041 | J:225200 | ||
