Phenotypes Associated with This Genotype

Genotype
MGI:2174731

• Allelic Composition: Scn8a^med/Scn8a^med
• Genetic Background: PCT

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

mortality/aging

postnatal lethality ( J:5153 , J:28678 , J:28679 )

• mice die within 2 weeks of onset of weakness (J:5153)

• most mice die by day 19 (J:28678)

• mice die at about 3 weeks of age (J:28679)

nervous system

abnormal neuromuscular synapse morphology ( J:5153 , J:28678 )

• motor nerves show marked terminal sprouting, the sprouts growing beyond the normal confines on the motor end-plates (J:5153)

• motor end plates become progressively more complex and elongated with fine branching of the nerve fiber within the region of motor terminal (J:28678)

• mice exhibit defects in neuromuscular transmission (J:28678)

demyelination ( J:6888 , J:7297 )

• most axons show signs of paranodal demyelination (J:6888)

• the demyelinated gaps of the nodes of Ranvier in the sciatic nerve are wider than in wild-type mice (J:7297)

abnormal action potential ( J:5192 )

• intracellular recordings from single muscle fibers show that with longer survival of the animal an increasing proportion of the fibers fail to show end-plate potentials or action potentials in response to nerve stimulation

abnormal nerve conduction ( J:6888 )

• conduction velocity is slower, the refractory period is prolonged and the temperature sensitivity is higher than in wild-type mice

abnormal endplate potential ( J:5192 )

• intracellular recordings from single muscle fibers show that with longer survival of the animal an increasing proportion of the fibers fail to show end-plate potentials or action potentials in response to nerve stimulation

abnormal miniature endplate potential ( J:5192 )

• the frequency of miniature endplate potentials is increased compared to in wild-type and is not increased by titanic stimulation

muscle

muscular atrophy ( J:5153 )

• mice exhibit progressive atrophy of skeletal muscle that is particularly severe in proximal limb muscles

abnormal muscle physiology ( J:5192 )

• muscles exhibit spontaneous fibrillation in isolated preparations

• muscles give only a weak twitch or fail to contract in response to nerve stimulation

• direct stimulation results in a twitch response that is slower than in wild-type muscles

• however, peripheral nerve conduction is normal

abnormal muscle tone ( J:28679 )

• at 1 week of age mice are softer and floppier than wild-type mice as if lacking muscle tone

progressive muscle weakness ( J:5153 , J:28678 )

• mice exhibit progressive weakness of skeletal muscle beginning at 8 to 10 days old (J:5153)

• beginning at day 9 mice exhibit progressive weakness and wasting of skeletal muscle (J:28678)

behavior/neurological

hindlimb paralysis ( J:28679 )

• mice exhibit progressive hindlimb paralysis

paraparesis ( J:28679 )

• mice become shaky as hindlimb function is lost and develop a seal-like movement with head going up and down