mortality/aging
• most mutant mice die after birth but a small fraction, 4%, survive
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nervous system
• expression analysis indicates that differentiation of dentate gyrus progenitors is impaired
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• no fibers are found crossing the dentate gyrus blades
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• cells appear to accumulate at the periphery of the dentate gyrus suggesting a defect in inward migration
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• at E15.5 and E16.5, the number of dentate gyrus progenitors labeled with BrdU after a 30 minute pulse is reduced by 20-25% in the primary and secondary matrices of null mice compared with wild-type controls
• however, the ratio of cells in S-phase to the number of dividing cells is similar to controls suggesting the decrease in proliferation is the result of a decrease in progenitor numbers and not a change in cell cycle length
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• granule neuron layer is disorganized when compared with control brains
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• absence of the dentate granule layer in perinatal stages (E18.5 and P1)
• the upper blade of the dentate gyrus is reduced in size and the lower blade is absent, in adults cells appear to accumulate at the periphery of the dentate gyrus suggesting a defect in inward migration
• absence of radial flial fibers crossing the blades
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• decrease in the number of GFP labeled progenitors in the secondary matrix at E16.5 and in the primary, secondary, and tertiary matrices at E18.5
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cellular
• expression analysis indicates that differentiation of dentate gyrus progenitors is impaired
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• no fibers are found crossing the dentate gyrus blades
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• cells appear to accumulate at the periphery of the dentate gyrus suggesting a defect in inward migration
|
• at E15.5 and E16.5, the number of dentate gyrus progenitors labeled with BrdU after a 30 minute pulse is reduced by 20-25% in the primary and secondary matrices of null mice compared with wild-type controls
• however, the ratio of cells in S-phase to the number of dividing cells is similar to controls suggesting the decrease in proliferation is the result of a decrease in progenitor numbers and not a change in cell cycle length
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