OBJECTIVES: Mutations in the @entity29732 subunit of the neuronal Na(+) /K(+) -ATPase are thought to be responsible for @entity410 , @entity1158 , and other symptoms of @entity4373 ( @entity4373 ). However, the mechanisms through which @entity68698 mutations mediate their pathophysiologic consequences are not yet understood. The following hypotheses were investigated: (1) Our novel knock-in @entity19 carrying the most common heterozygous mutation causing @entity4373 ( @entity29736 ) will exhibit the manifestations of the @entity1 condition and display predisposition to @entity410 ; and (2) the underlying pathophysiology in this @entity19 model involves @entity101 in response to electrical stimulation of Schaffer collaterals and abnormal predisposition to @entity308 ( @entity308 ). METHODS: We generated the @entity29736 mutant @entity19 (Mashlool, Mashl(+/-) ) and compared mutant and wild-type (WT) littermates. Behavioral tests, amygdala kindling, @entity15945 -induced @entity410 threshold, @entity410 ( @entity410 ), and other paroxysmal activities were compared between groups. In vitro electrophysiologic slice experiments on hippocampus were performed to assess predisposition to hyperexcitability and @entity308 . RESULTS: Mutant @entity19 manifested a distinctive phenotype similar to that of @entity1 with @entity4373 . They had abnormal impulsivity, memory, gait, motor coordination, @entity400 , motor control, endogenous nociceptive response, paroxysmal @entity1158 , @entity306 , @entity3519 , and @entity410 , as well as predisposition to kindling, to @entity15945 -induced @entity410 , and to sudden unexpected @entity204 . Hippocampal slices of mutants, in contrast to WT animals, showed hyperexcitable responses to 1  Hz pulse-trains of electrical stimuli delivered to the Schaffer collaterals and had significantly longer duration of K(+) -induced @entity308 responses. SIGNIFICANCE: Our model reproduces the major characteristics of @entity1 @entity4373 , and indicates that @entity29732 dysfunction results in abnormal short-term plasticity with @entity101 (potential mechanism for @entity410 ) and a predisposition to more severe @entity308 responses (potential mechanism for @entity1158 ). This model of the @entity1 condition should help in understanding the molecular pathways underlying these phenotypes and may lead to identification of novel therapeutic strategies of @entity29732 related disorders and @entity410 .

Knock-in XXXX model of @entity4373 : Behavioral and electrophysiologic characterization.

@entity1158 :: ('MESH:D006429', 'Disease') :: ['hemiplegias'] @entity1 :: ('9606', 'Species') :: ['humans', 'human'] @entity410 :: ('MESH:D012640', 'Disease') :: ['seizure', 'SRS', 'spontaneous recurrent seizures', 'seizures'] @entity308 :: ('MESH:D003866', 'Disease') :: ['SD', 'spreading depression'] @entity68698 :: ('232975(Tax:10090)', 'Gene') :: ['ATP1A3'] @entity101 :: ('MESH:D006973', 'Disease') :: ['increased excitability'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity4373 :: ('MESH:C536589', 'Disease') :: ['AHC', 'alternating hemiplegia of childhood'] @entity29732 :: ('478', 'Gene') :: ['ATP1a3'] @entity29736 :: ('p|SUB|D|801|N', 'ProteinMutation') :: ['D801N'] @entity15945 :: ('MESH:D005481', 'Chemical') :: ['flurothyl'] @entity400 :: ('MESH:D014202', 'Disease') :: ['tremor'] @entity3519 :: ('MESH:D004421', 'Disease') :: ['dystonias'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death'] @entity306 :: ('MESH:D002547', 'Disease') :: ['diplegias']
@entity19 :: (10090,Species) :: ['mouse']
