Phenotypes Associated with This Genotype

Genotype
MGI:3690092

• Allelic Composition: Scn1a^tm1Wac/Scn1a^tm1Wac
• Genetic Background: B6.129-Scn1a^tm1Wac

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

postnatal lethality, complete penetrance ( J:113149 )

• homozygotes die by P15; treatment with diazepam decreases seizure frequency but does not extend survival past P15

behavior/neurological

abnormal postural reflex ( J:113149 )

• problems progress to complete loss of postural control

impaired righting response ( J:113149 )

• at P15, mice require longer to recover from supine to prone position than wild-type and display a pronounced lack of coordination

tremors ( J:113149 )

• beginning at P9, neurological abnormalities progress to include mild limb tremors

ataxia ( J:113149 )

• beginning at P9, mutants exhibit ataxia

abnormal posture ( J:113149 )

• beginning at P9, neurological abnormalities progress to include side-to-side swaying

akinesia ( J:113149 )

• by P15, mutants become inactive except for periodic seizure activity

seizures ( J:113149 )

• beginning at P9, mutants exhibit seizures which progress in severity

convulsive seizures ( J:113149 )

• at P15, mice exhibit bilateral forelimb convulsive seizures

clonic seizures ( J:113149 )

• at P15, mice display generalized clonic seizures

nervous system

seizures ( J:113149 )

• beginning at P9, mutants exhibit seizures which progress in severity

convulsive seizures ( J:113149 )

• at P15, mice exhibit bilateral forelimb convulsive seizures

clonic seizures ( J:113149 )

• at P15, mice display generalized clonic seizures

abnormal nervous system electrophysiology ( J:113149 )

• isolated hippocampal pyramidal neurons show a substantial decrease in sodium current levels

• current densities in homozygotes (pA = 41 pA/pF) are decreased compared to wild-type (pA = 149 pA/pF)

abnormal action potential ( J:113149 )

• amplitude of the action potential is reduced and width is increased in response to injection of depolarizing current compared to wild-type interneurons

• peak of action potential is greater and minimum voltage after the action potential is more negative in wild-type compared to mutant interneurons