Analysis Tools
mortality/aging
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• most homozygotes died around 14 days of age (P14), none survived past P21
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behavior/neurological
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• relative to wild-type, mutants displayed a lower threshold for pentylenetetrazol-induced seizures
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abnormal gait
(
J:77297
)
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• at P12, mutants showed a wide, uncoordinated gait, and frequently fell on their backs while walking
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• at P12, mutants started to exhibit lethal seizures, typified by myoclonic jerks, loss of posture, and hyperextension of the trunk and hindlimbs
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growth/size/body
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• at ~P10, mutants began to exhibit failure to thrive
• at P12, mutants weighed 20% less than wild-type
• no correlation between mortality and reduced growth rate was observed
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muscle
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• at P12, mutants started to exhibit lethal seizures, typified by myoclonic jerks, loss of posture, and hyperextension of the trunk and hindlimbs
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reproductive system
| N |
• the ovaries of mutant females appeared histologically normal
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• mutant males exhibited embryonic and postnatal loss of undifferentiated germ cells
• the specification and migration of primordial germ cells appeared normal; however, the number of spermatogenic precursors was markedly reduced as early as E12.5
• in the first postnatal days, gonocytes and type A spermatogonia were still present but their number was severely reduced
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• in mutant testes, cellular depletion was caused by increased apoptosis of undifferentiated and differentiating precursors
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• gonocytes and spermatogonia with multiple nuclei were produced in the seminiferous tubules indicating a cytokinesis block
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nervous system
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• relative to wild-type, mutants displayed a lower threshold for pentylenetetrazol-induced seizures
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• at P12, mutants started to exhibit lethal seizures, typified by myoclonic jerks, loss of posture, and hyperextension of the trunk and hindlimbs
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• in mutant brains, depletion of specific microneurons in the olfactory bulb, hippocampus and cerebellum was caused by aberrant cytokinesis and massive apoptosis
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• at P14, the overall average weight of mutant brains was reduced by 50%
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• mutants displayed an average reduction of ~20% in the mesencephalon
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• mutants displayed an average reduction of ~20% in the diencephalon and midbrain
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• mutants displayed an average reduction of 50% in the cerebral hemispheres
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• the dentate gyrus was almost completely absent
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• in the mutant olfactory bulbs, the periglomerular interneurons, olfactory granular cells, and the external plexiform layer were almost completely absent
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• mutants displayed an average reduction of 70% in the olfactory bulbs
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• the monolayer architecture of Purkinje cells appeared disorganized with abnormal dendritic arborization
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• the granule cell layer was significantly reduced
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• in the mutant cerebellum, all major lobules were smaller than wild-type
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• mutants displayed an average reduction of 70% in the cerebellum
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cellular
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• mutant males exhibited embryonic and postnatal loss of undifferentiated germ cells
• the specification and migration of primordial germ cells appeared normal; however, the number of spermatogenic precursors was markedly reduced as early as E12.5
• in the first postnatal days, gonocytes and type A spermatogonia were still present but their number was severely reduced
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• in mutant testes, cellular depletion was caused by increased apoptosis of undifferentiated and differentiating precursors
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• in mutant brains, depletion of specific microneurons in the olfactory bulb, hippocampus and cerebellum was caused by aberrant cytokinesis and massive apoptosis
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• gonocytes and spermatogonia with multiple nuclei were produced in the seminiferous tubules indicating a cytokinesis block
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