Phenotypes associated with this allele

• Allele Symbol: Scn4a^m1Aaa
• Allele Name: mutation 1, Abraham Acevedo-Arozena
• Allele ID: MGI:5308659
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Scn4a^m1Aaa/Scn4a^m1Aaa	involves: BALB/c * C57BL/6J	MGI:5614554
ht2	Scn4a^m1Aaa/Scn4a^+	involves: BALB/c * C57BL/6J	MGI:5614553
ht3	Scn4a^m1Aaa/Scn4a^tm1.1Ljh	involves: 129S4/SvJae * BALB/c * C57BL/6J	MGI:5614555

Genotype
MGI:5614554

hm1

• Allelic Composition: Scn4a^m1Aaa/Scn4a^m1Aaa
• Genetic Background: involves: BALB/c * C57BL/6J

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

mortality/aging

perinatal lethality, complete penetrance ( J:217522 )

• die by 2 days of age although born in expected numbers

• perinatal death with breathing difficulties and collapsed lungs

muscle

muscle phenotype ( J:217522 )

N • muscles are morphologically normal

respiratory system

abnormal lung volume ( J:217522 )

• collapsed lungs

respiratory distress ( J:217522 )

• difficulty breathing

Genotype
MGI:5614553

ht2

• Allelic Composition: Scn4a^m1Aaa/Scn4a⁺
• Genetic Background: involves: BALB/c * C57BL/6J

mortality/aging

mortality/aging ( J:217522 )

N • normal life span

behavior/neurological

impaired coordination ( J:217522 )

• progressive deterioration in motor coordination

abnormal grip strength ( J:217522 )

• progressive deterioration

akinesia ( J:217522 )

• intermittent hind-limb immobility

• total recovery after a few seconds

• average onset of episodes is around 16 weeks in males and 25 weeks in females

• earliest onset is around weaning and the latest is around 60 weeks

• number of attacks is greater in males than in females

muscle

abnormal muscle morphology ( J:217522 )

abnormal muscle fiber morphology ( J:217522 )

• fibers in tibialis anterior switch to more oxidative type fibers as early as 12 weeks in age

• progressive muscle pathology at 1.5 years by electron microscopy

• tubular aggregates and irregular triads

increased skeletal muscle fiber size ( J:217522 )

• in 60 week old muscles

centrally nucleated skeletal muscle fibers ( J:217522 )

• increased in 60 week old muscles

abnormal muscle physiology ( J:217522 )

impaired skeletal muscle contractility ( J:217522 )

• time of maximum contraction is significantly higher in 60 week tibialis anterior and extensor digitorum muscles

• high potassium levels result in significant force reduction

abnormal muscle electrophysiology ( J:217522 )

• striking myotonic runs after light movement detected by electromyography regardless of the occurrence of immobility episodes

• intense EMG activity during immobility attacks

impaired muscle relaxation ( J:217522 )

• time of half relaxation is significantly higher in 60 week tibialis anterior and extensor digitorum muscles

increased muscle fatigability ( J:217522 )

• 60 week extensor digitorum is more fatigue resistant

muscle twitch ( J:217522 )

• single twitch force and maximum force are reduced

growth/size/body

slow postnatal weight gain ( J:217522 )

♂ • significantly reduced weight gain after 12 weeks for males but not females

♂ • less total fat but normal food consumption

homeostasis/metabolism

decreased circulating leptin level ( J:217522 )

• at 40 weeks of age

increased energy expenditure ( J:217522 )

• higher whole body energy expenditure in the dark period controlling for total body weight

improved glucose tolerance ( J:217522 )

• relative to controls

Genotype
MGI:5614555

ht3

• Allelic Composition: Scn4a^m1Aaa/Scn4a^tm1.1Ljh
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6J

mortality/aging

perinatal lethality, complete penetrance ( J:217522 )

respiratory system

abnormal lung volume ( J:217522 )

respiratory distress ( J:217522 )

muscle

muscle phenotype ( J:217522 )

N • muscles are morphologically normal