Analysis Tools
nervous system
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• homozygotes are viable and overtly normal, with no gross morphological defects in the cerebellum, spinal cord, or hippocampus relative to wild-type mice
• surprisingly, the thickness and density of both the granular cell layer and the Purkinje cell layer of the cerebellum are unaffected at E15 and P2, and no changes in the pathways of the spinal commissural axons are observed at P2
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• despite normal hippocampal histology (at E15, P2, and P34), homozygotes show increased susceptibility to pentylenetetrazole (PTZ)- and kainic acid-induced seizures relative to wild-type control mice
• whereas administration of 30 mg/kg of PTZ fails to induce convulsive behavior in wild-type mice, it induces clonic-tonic seizures in 52% of similarly-treated mutant mice
• in response to 20 mg/kg kainic acid, mutant mice display normal changes in motor behavior (including myoclonic twitching in the head, face and fore-limbs that often develops into generalized clonic-tonic seizures) relative to wild-type mice; however, mutant mice show significantly shorter latencies to generalized seizures, a signicantly prolonged convulsive phase (with frequent rearing, falling over to one side, and oral foam) and a mortality rate of >75% within 24 hrs post-treatment relative to <10% in wild-type mice
• increased sensitivity to convulsant stimuli is attributed to a 40% increase in adenosine A1 receptors in the hippocampus and other subtle changes in neural plasticity during development
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• although homozygotes are behaviorally normal and exhibit no signs of ataxia, a few display spontaneous epileptic seizures
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behavior/neurological
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• despite normal hippocampal histology (at E15, P2, and P34), homozygotes show increased susceptibility to pentylenetetrazole (PTZ)- and kainic acid-induced seizures relative to wild-type control mice
• whereas administration of 30 mg/kg of PTZ fails to induce convulsive behavior in wild-type mice, it induces clonic-tonic seizures in 52% of similarly-treated mutant mice
• in response to 20 mg/kg kainic acid, mutant mice display normal changes in motor behavior (including myoclonic twitching in the head, face and fore-limbs that often develops into generalized clonic-tonic seizures) relative to wild-type mice; however, mutant mice show significantly shorter latencies to generalized seizures, a signicantly prolonged convulsive phase (with frequent rearing, falling over to one side, and oral foam) and a mortality rate of >75% within 24 hrs post-treatment relative to <10% in wild-type mice
• increased sensitivity to convulsant stimuli is attributed to a 40% increase in adenosine A1 receptors in the hippocampus and other subtle changes in neural plasticity during development
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• although homozygotes are behaviorally normal and exhibit no signs of ataxia, a few display spontaneous epileptic seizures
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