mortality/aging
• most mice die between P0 and P10 with some mice surviving until P20
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nervous system
• neurons and their precursors in the cortex and subventricular zone undergo more apoptosis than in wild-type mice
• however, hippocampal cells do not undergo apoptosis except for those located in the lateral ventricle
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• in culture, neurospheres differentiate into GFAP+ cells that have astrocyte-like morphology unlike wild-type neurospehre cells
• in the presence of PDGF more neurospheres differentiated into GFAP+ cells (47.0+/-1.5% compared to 31.6+/-4.8% of wild-type neurospheres) while in the presence of BDNF fewer do so (21.6+/-5.8% compared to 25.6+/-5.2 of wild-type neurospheres)
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• neuron migration is impaired and in culture neurons move 8 to 15% slower than wild-type neurons when plated on laminin
• however, proliferation and differentiation of neurons is normal
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• at P0 the rostral migratory stream is thicker than in wild-type mice but by P10 it is thinner than in wild-type mice
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• GABAnergic interneurons in the cerebral cortex are decreased to 20% of the number found in wild-type mice
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• hippocampal cells located in the lateral ventricle undergo apoptosis
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• coronal and sagittal brain sections reveal an increase in the size of the lateral ventricle as well as a thinner cortex
• lateral ventricles increase with age
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• the corpus callosum is thinner than in wild-type mice or partially absent
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• the striatum is thinner than in wild-type mice
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• the diencephalons is thinner than in wild-type mice
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• hippocampal cells located in the lateral ventricle undergo apoptosis
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• mice have fewer cortical cells than in wild-type mice
• neurons and their precursors in the cortex and subventricular zone undergo more apoptosis than in wild-type mice
• GABAnergic interneurons in the cerebral cortex are decreased to 20% of the number found in wild-type mice
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• in layers II/III and IV of the neocortex
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• unlike in wild-type mice, pyramidal cells are detected in the subventricular zone
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• coronal and sagittal brain sections reveal an increase in the size of the lateral ventricle as well as a thinner cortex
• the cerebral cortex becomes thinner with age
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• at P10, the olfactory bulb is smaller than in wild-type mice due to impaired movement of neuroblasts from the sub-ventricular zone to the olfactory bulb
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• neurons and their precursors in the cortex and subventricular zone undergo more apoptosis than in wild-type mice
• unlike in wild-type mice, pyramidal cells are detected in the subventricular zone
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• glial cell migration is impaired whereby GFAP+ cells are confined to the subventricular zone close to the lateral ventricle
• unlike in wild-type mice, GFAP+ cells exhibit an elongated morphology
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• the number of GFAP+ astrocytes in the hippocampus is decreased to 30% of wild-type hippocampus
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behavior/neurological
• mice exhibit slow, weak and uncoordinated movements
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growth/size/body
• mice are smaller than normal
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cellular
• neurons and their precursors in the cortex and subventricular zone undergo more apoptosis than in wild-type mice
• however, hippocampal cells do not undergo apoptosis except for those located in the lateral ventricle
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• in culture, neurospheres differentiate into GFAP+ cells that have astrocyte-like morphology unlike wild-type neurospehre cells
• in the presence of PDGF more neurospheres differentiated into GFAP+ cells (47.0+/-1.5% compared to 31.6+/-4.8% of wild-type neurospheres) while in the presence of BDNF fewer do so (21.6+/-5.8% compared to 25.6+/-5.2 of wild-type neurospheres)
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• neuron migration is impaired and in culture neurons move 8 to 15% slower than wild-type neurons when plated on laminin
• however, proliferation and differentiation of neurons is normal
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