Phenotypes associated with this allele

• Allele Symbol: Scn8a^med
• Allele Name: motor end plate disease
• Allele ID: MGI:1856078
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Scn8a^med/Scn8a^med	involves: C3HeB/FeJ * DBA/2J	MGI:3818085
hm2	Scn8a^med/Scn8a^med	PCT	MGI:2174731
ht3	Scn8a^med/Scn8a^+	C3Fe.Cg-Scn8a^med/J	MGI:3818171
ht4	Scn8a^dmu/Scn8a^med	involves: C3H * C3HeB/Fe * C57BL/6	MGI:3818076

Genotype
MGI:3818085

hm1

• Allelic Composition: Scn8a^med/Scn8a^med
• Genetic Background: involves: C3HeB/FeJ * DBA/2J

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

vision/eye

abnormal eye electrophysiology ( J:98511 )

• at P16, alpha and beta waves are reduced and latency times are increased compared to in wild-type mice

Genotype
MGI:2174731

hm2

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

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

Genotype
MGI:3818171

ht3

• Allelic Composition: Scn8a^med/Scn8a⁺
• Genetic Background: C3Fe.Cg-Scn8a^med/J

behavior/neurological

decreased susceptibility to pharmacologically induced seizures ( J:129998 )

• following exposure to flurothyl, mice exhibit a 25% increase in latency to myoclonic jerk and a 58% increase in latency to generalized tonic-clonic seizure (GTCS) compared to in similarly treated wild-type mice

• following exposure to kainic acid, mice exhibit reduced seizure severity and no GTCS compared to similarly treated wild-type mice

abnormal spike wave discharge ( J:147199 )

• mice exhibit spike wave discharge (SWD) accompanied by behavior arrest unlike wild-type mice

• the average incidence of SWD is higher than in Scn8a^med heterozygotes but lower than in Scn8a^8J heterozygotes

• ethosuximide treatment results in 11-fold fewer and shorter SWD compared to a 3-fold increase in frequencies following saline treatment

• the frequency of SWD during slow-wave sleep and paradoxical SWD are higher during the dark cycle than during the light cycle

nervous system

decreased susceptibility to pharmacologically induced seizures ( J:129998 )

• following exposure to flurothyl, mice exhibit a 25% increase in latency to myoclonic jerk and a 58% increase in latency to generalized tonic-clonic seizure (GTCS) compared to in similarly treated wild-type mice

• following exposure to kainic acid, mice exhibit reduced seizure severity and no GTCS compared to similarly treated wild-type mice

abnormal spike wave discharge ( J:147199 )

• mice exhibit spike wave discharge (SWD) accompanied by behavior arrest unlike wild-type mice

• the average incidence of SWD is higher than in Scn8a^med heterozygotes but lower than in Scn8a^8J heterozygotes

• ethosuximide treatment results in 11-fold fewer and shorter SWD compared to a 3-fold increase in frequencies following saline treatment

• the frequency of SWD during slow-wave sleep and paradoxical SWD are higher during the dark cycle than during the light cycle

Genotype
MGI:3818076

ht4

• Allelic Composition: Scn8a^dmu/Scn8a^med
• Genetic Background: involves: C3H * C3HeB/Fe * C57BL/6

mortality/aging

postnatal lethality ( J:71615 )

• mice do not survive beyond weaning

muscle

dystrophic muscle ( J:71615 )

• beginning at 2 weeks of age although a few days later than in Scn8a^dmu homozygotes

behavior/neurological

abnormal voluntary movement ( J:71615 )

• similar to Scn8a^med homozygotes, mice are prone to positioning themselves on their side and wriggling

hindlimb paralysis ( J:71615 )

• at 2 weeks of age mice exhibit a progressive loss of mobility in their hindlimbs