Phenotypes Associated with This Genotype

Genotype
MGI:3625870

• Allelic Composition: Kcna1^tm1Tem/Kcna1^tm1Tem
• Genetic Background: C3Fe.129S7-Kcna1^tm1Tem

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

behavior/neurological

decreased chemical nociceptive threshold ( J:107933 )

• mutants display greater pain behavior in response to formalin injection; total paw licking time is greater in mutants

decreased chemically-elicited antinociception ( J:107933 )

• effects of subcutaneous morphine is attenuated in mutants compared to wild-type, as assessed by increase in latency in the thermal pain assays

decreased thermal nociceptive threshold ( J:107933 )

• mutant animals show reduced latencies in 2 thermal pain assays; in response to a focused light beam on the hind paw and in a hot plate assay, mutants more quickly display a paw flick or paw lick, respectively

seizures ( J:206598 )

• mice develop seizures by P21

• mice treated with AATP (combination treatment of ascorbic acid, alpha-tocopherol and sodium pyruvate) show reduced seizure burden

nervous system

seizures ( J:206598 )

• mice develop seizures by P21

• mice treated with AATP (combination treatment of ascorbic acid, alpha-tocopherol and sodium pyruvate) show reduced seizure burden

abnormal nervous system electrophysiology ( J:105296 )

• low voltage activated K+ currents are significantly smaller than controls

abnormal action potential ( J:105296 )

• action potentials are generated to very small current clamp steps

• threshold about 48 pA as opposed to 90pA for controls

• two times as many action potentials generated as by controls

decreased nerve fiber response threshold ( J:105296 )

decreased paired-pulse ratio ( J:206598 )

• paired-pulse ratios are 51% lower at the mossy fiber-CA3 synapses following paired-pulse stimulations and field potential slopes are about 225% larger than in wild-type mice

• mice treated with AATP show improved mossy fiber CA3-paired pulse ratios but does not influence the field potential slopes

cellular

abnormal mitochondrial ATP synthesis coupled electron transport ( J:206598 )

• mice show reduced mitochondrial respiratory complex I respiratory rates: ATP-producing state III respiration is diminished by 32% in cortical and 36% in hippocampal mitochondria and the maximal rate of the electron transport (state V) is reduced in both cortical and hippocampal mitochondria, indicating that mitochondria consume less oxygen

• UCP2 protein levels are reduced by 20% in mitochondria and functional uncoupling is reduced by 68%, indicating a loss of function of the protein machinery that promotes successful electron transport

• mice treated with AATP show improved mitochondrial functions

oxidative stress ( J:206598 )

• the reduced mitochondrial respiratory complex I-driven respiratory rates are associated with a 20% increase in hydrogen peroxide levels in the cortex and a 35% increase in the hippocampus, indicating an elevation of reactive oxygen species (ROS) is mitochondria

• mice treated with AATP show a reduction of ROS by 14% in the hippocampus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
temporal lobe epilepsy		DOID:3328	OMIM:PS600512	J:206598