Analysis Tools
behavior/neurological
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• adult homozygotes exhibited an increased susceptibility to kainic acid-induced limbic seizures by reaching stage 6 tonic-clonic convulsion faster than wild-type mice, and developed several seizures during the 45-min observation period while most wild-type mice developed only one stage 6 tonic-clonic convulsion
• at a high dosage of KA (25 mg/kg), 4 out of 7 homozygotes died after continuous tonic-clonic convulsions compared with only 1 of 8 wild-type mice
• at a lower dosage of KA (15 mg/kg), 6 of 8 homozygotes and only 2 of 9 wild-type mice developed seizures
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• homozygotes were viable and overtly normal; however, 6 of 18 mice failed a contact-righting test, but behaved similar to controls in an elevated-platform, reaching response and swimming tests
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hyperactivity
(
J:73971
)
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• by 3 weeks of age, abnormal hyperactive behavior was seen in 15% of mice
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• by 3 weeks of age, partial bidirectional circling behavior was seen in 15% of mice
• circling behavior was interspersed with noncircling periods of feeding, grooming, and sleep
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• a small % of adult homozygotes displayed brief freezing spells with tonic posturing that were exacerbated with handling
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hearing/vestibular/ear
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• reduced diameter of semicircular canals apparent by E16.5, also noted at P1
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• diminished endolymphatic space
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• roof of ampullas appear flattened at E16.5 and at P1
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• abnormal vestibular function due to defective outgrowth of the semicircular canals of the inner ear
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nervous system
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• adult homozygotes exhibited an increased susceptibility to kainic acid-induced limbic seizures by reaching stage 6 tonic-clonic convulsion faster than wild-type mice, and developed several seizures during the 45-min observation period while most wild-type mice developed only one stage 6 tonic-clonic convulsion
• at a high dosage of KA (25 mg/kg), 4 out of 7 homozygotes died after continuous tonic-clonic convulsions compared with only 1 of 8 wild-type mice
• at a lower dosage of KA (15 mg/kg), 6 of 8 homozygotes and only 2 of 9 wild-type mice developed seizures
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• a small % of adult homozygotes displayed brief freezing spells with tonic posturing that were exacerbated with handling
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• small but significant increase of apoptosis in CA1 pyramidal neurons as early as P0, with maximal cell death noted at P5
• by P7, apoptosis in CA1 pyramidal cell layer was decreased to the level of wild-type mice
• no cellular loss due to apoptosis was observed in the CA3 region
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• reduced outgrowth of granule cell mossy fibers into CA3 stratum lucidum, noted at P7, P14 and through adulthood
• reduced outgrowth of mossy cell axons into the suprapyramidal blade in the inner molecular layer of the dentate gyrus, noted at P14 and through adulthood
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• abnormal postnatal axonal guidance of dentate gyrus granule and mossy cells
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• abnormal early postnatal hippocampal development due to defective hippocampal axonal growth and postnatal neuronal cell death
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• absence of a compact pyramidal cell layer of Ammon's horn, as shown at the levels of CA3 and CA1
• pyramidal cell layer disorganization both at the level of CA3 and CA1, evident at P7 and exacerbated at P14 and P21
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• significant reduction in the total number of pyramidal cells in the CA1 region but not in the CA3 region of the hippocampus
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• loss of pyramidal CA1 neurons during early postnatal stages of development, with maximal loss at P14 and P21 that persists to adulthood
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cellular
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• small but significant increase of apoptosis in CA1 pyramidal neurons as early as P0, with maximal cell death noted at P5
• by P7, apoptosis in CA1 pyramidal cell layer was decreased to the level of wild-type mice
• no cellular loss due to apoptosis was observed in the CA3 region
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• reduced outgrowth of granule cell mossy fibers into CA3 stratum lucidum, noted at P7, P14 and through adulthood
• reduced outgrowth of mossy cell axons into the suprapyramidal blade in the inner molecular layer of the dentate gyrus, noted at P14 and through adulthood
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• abnormal postnatal axonal guidance of dentate gyrus granule and mossy cells
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