Analysis Tools
mortality/aging
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• abnormal Mendelian ratio and sex ratio are observed in the progeny of heterozygote outcrosses, with both stillbirth and neonatal death
• fewer than the expected number of males are obtained
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growth/size/body
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• mice weigh less at early time points (P7 to around P21) but dramatically increase afterward
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• mice show increased weight starting around P30 and up to P300
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nervous system
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• cleaved caspase 3 and NeuN-double-positive cell levels are increased in the cortices and TUNEL+ cells are increased indicating increased neuronal apoptosis
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• increase in number of microglia in the cortices of adults
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• surviving mice exhibit cerebral cortex cortical developmental malformations
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• in the cortices of adults
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astrocytosis
(
J:323615
)
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• both brain hemispheres exhibit increased astrocytosis
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• aborted mice exhibit neurodevelopmental delay
• surviving mice show impaired cortical neurogenesis and adult lineage choice
• intermediate progenitor cells are reduced during neurogenesis
• imbalance of neuronal versus glial lineage differentiation is seen, with increased numbers of astrocytes and microglia in the cortices of adults and decreased neuron numbers
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• intermediate progenitor cell-to-mature neuron transition is reduced resulting in distinct lineage outcomes in the adult cortex
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• TBR2+ cells are dysregulated in the subventricular zone (SVZ) beginning at E14.5
• ectopic expression of Pax6 is seen in the VZ/SVZ of E14.5 brains, indicating ectopic apical neural progenitor cells
• decrease in the percentage of mitotic cells in the VZ/SVZ regions of E14.5 brain, indicating decreased cell proliferation in the cerebral cortex
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• decrease in neuron number in the cortices of adults
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embryo
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• 13% arrest of embryonic development
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behavior/neurological
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• mice spend less time in the open arms of the elevated plus-maze
• mice show limited curiosity, spending less time in the light chamber in the light-dark transition test than wild-type mice
• however, no differences in the distance traveled in the center and time spent in the center area in the Morris water maze were seen, indicating normal learning
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• mice arrive at the center zone less frequently than wild-type mice in the open field test
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• in the novel object preference test, mice show decreased preference for a new object
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• in the social novelty preference test, mice show less preference for stranger 2 than wild-type mice
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• mice show more prolonged bouts of self-grooming
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• mice show motor coordination and balance deficits on the rotarod
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• in the three-chambered test, mice lack interest in interaction with stranger mice
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hematopoietic system
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• increase in number of microglia in the cortices of adults
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immune system
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• increase in number of microglia in the cortices of adults
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cellular
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• cleaved caspase 3 and NeuN-double-positive cell levels are increased in the cortices and TUNEL+ cells are increased indicating increased neuronal apoptosis
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• intermediate progenitor cell-to-mature neuron transition is reduced resulting in distinct lineage outcomes in the adult cortex
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