Analysis Tools
mortality/aging
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• mice typically die within 48 hours of seizure onset following a fatal seizure ending in tonic hindlimb extension, with the majority dying prior to weaning age of P21
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growth/size/body
behavior/neurological
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• P8-P10 mice exhibit reduced ability to right, with some mice unable to right themselves at all during the 60 sec trial
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• P8-P16 mice that have not exhibited seizures show unbalanced gait with severe tremors
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• P8-P14 mice spend less time hanging from either frontlimbs or hindlimbs
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• P8-P16 mice that have not exhibited seizures show unbalanced gait with severe tremors and more falls on P9 and P10 and mice never achieve balance gait, indicating motor impairment prior to seizure onset
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• mice develop generalized tonic-clonic seizures as early as P13
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muscle
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• compound muscle action potentials from the right triceps surae at P11 are reduced
• the motor unit number estimation (electrophysiologic estimation of the number of motor units in a particular muscle) is reduced, indicating that there are fewer functional motor units
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nervous system
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• mice develop generalized tonic-clonic seizures as early as P13
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• gastrocnemius muscle exhibits morphological alternations in the neuromuscular junction (NMJ) at P15, with smaller perimeters of presynaptic nerve terminals, reduced branching complexity, smaller endplates, reduced acetylcholine receptor area and NMJ compactness, and reduced synaptic contact in NMJs
• reduction in size and branching complexity of the NMJ suggests that NMJ maturation is delayed, however the majority of NMJs are monoinnervated, indicating that maturation is not arrested completely
• however, no differences in axon diameter at innervated NMJs is seen and there are no signs of NMJ degeneration at P15
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• prior to biasing the membrane potential to -70 mV, CA1 pyramidal cells have a depolarized resting potential
• CA1 pyramidal cells have a greater voltage sag, indicating larger h-current (hyperpolarization-activated cationic current) and greater expression of HCN channels
• CA1 pyramidal neurons have a lower membrane capacitance in response to 10 pA current pulses
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• CA1 pyramidal cells are hyperexcitable, with the majority firing at least two action potentials and some firing bursts of 3 or more
• CA1 pyramidal neurons exhibit a lower rheobase current for action potential initiation but the voltage threshold is not different, most likely due to an increase in input resistance
• at 1.5 times the rheobase current amplitude, most CA1 pyramidal neurons fire at least 2 action potentials, and many fire ectopic bursts of 3 or more and at each current step, cells fire more action potentials than those in controls
• spontaneous action potentials are seen prior to biasing the resting potential to -70 mV
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| developmental and epileptic encephalopathy 13 | DOID:0080445 |
OMIM:614558 |
J:383178 | |
