Phenotypes associated with this allele

• Allele Symbol: Scn4a^tm1Ljh
• Allele Name: targeted mutation 1, Lawrence J Hayward
• Allele ID: MGI:3763891
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Scn4a^tm1Ljh/Scn4a^tm1Ljh	B6.129S4-Scn4a^tm1Ljh	MGI:4420394
ht2	Scn4a^tm1Ljh/Scn4a^+	B6.129S4-Scn4a^tm1Ljh	MGI:4420395

Genotype
MGI:4420394

hm1

• Allelic Composition: Scn4a^tm1Ljh/Scn4a^tm1Ljh
• Genetic Background: B6.129S4-Scn4a^tm1Ljh

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

mortality/aging

decreased survivor rate ( J:135831 )

• by 30 days, 1.4% of pups are homozygotes, rather than the expected 25%

perinatal lethality, incomplete penetrance ( J:135831 )

• lethality observed in some pups by postnatal day 1

muscle

abnormal skeletal muscle fiber morphology ( J:135831 )

• large vacuolar structures containing a pale amorphous material are observed in muscle fibers

increased variability of skeletal muscle fiber size ( J:135831 )

• increased fiber size variation and frequent internalized nuclei are observed by 2.8 months of age

skeletal muscle atrophy ( J:135831 )

• fixed limb weakness with muscle atrophy

muscle weakness ( J:135831 )

• fixed limb weakness with muscle atrophy

myopathy ( J:135831 )

behavior/neurological

limb grasping ( J:135831 )

• abnormal hind-limb clasping behavior

growth/size/body

decreased body weight ( J:135831 )

• females weigh 16.6 grams by 2.8 months of age in contrast to controls (21.4 grams)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hyperkalemic periodic paralysis		DOID:14451	OMIM:170500	J:135831

Genotype
MGI:4420395

ht2

• Allelic Composition: Scn4a^tm1Ljh/Scn4a⁺
• Genetic Background: B6.129S4-Scn4a^tm1Ljh

muscle

abnormal skeletal muscle fiber morphology ( J:135831 )

increased variability of skeletal muscle fiber size ( J:135831 )

• fiber size variation and the presence of internalized nuclei are first observed at 4 months of age, becoming increasingly abnormal with age

abnormal muscle physiology ( J:135831 )

• muscle fibers from tibialis anterior, quadriceps and gastrocnemius muscles switch from a mix of glycolytic and oxidative fibers to an increased number of oxidative fibers typical of chronic muscle activity

impaired skeletal muscle contractility ( J:135831 )

• twitch force elicited by direct stimulation of muscle in 8-14 month old mice is 44% of that generated by the control; in younger mice (3-5 month) twitch force is 72%

• under tetanic stimulation, kinetics of force buildup and muscle relaxation from last stimulus are prolonged (110% vs 54% and 39% vs 30%, respectively)

• tetanic force is 34% less in 8-14 months old mice during 100-Hz stimulation compared in control

• peak tetanic force under increased K+ (8mM) conditions is decreased by 46%, while control is increased by 3%

• 88% loss of force is observed under increased K+ (10 mM) conditions as compared to control (9%), in addition, lowering Ca2+ increases weakness, but does not alter recovery time

• tetanic force is further decreased by administration of ouabain (a Na+/K+ pump inhibitor) under increased K+ conditions

impaired muscle relaxation ( J:135831 )

• robust myotonia is observed in hind limbs muscles by one month of age

• increased muscle irritability during electromyography in response to needle movement

increased muscle relaxation ( J:135831 )

• time to relaxation is increased by 69% following direct stimulation compared to control in 8 - 14 month old mice, however, younger (3-5 month) mice do not differ significantly from control

• under tetanic stimulation, kinetics of force buildup and muscle relaxation from last stimulus are prolonged (110% vs 54% and 39% vs 30%, respectively)

increased muscle fatigability ( J:135831 )

• induced fatigue of isolated extensor digitorum longus (EDL) results in delayed weakness (time required for 50% decline in force) and prolonged recovery compared to control

muscle weakness ( J:135831 )

myopathy ( J:135831 )

• mild myopathy is observed at 4 months; scattered internalized nuclei suggest regeneration by satellite cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hyperkalemic periodic paralysis		DOID:14451	OMIM:170500	J:135831