Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator Lawrence J Hayward,   University of Massachusetts Medical School

Description
Most homozygous mice die before 30 days, although a few live longer. Homozygotes appear smaller, have difficulty feeding, and exhibit an accelerated myopathy characterized by increased fiber size variation and vacuolar structures within muscle fibers. Mice heterozygous for the mutation exhibit continuous myotonia of skeletal muscles, progressive age-related myopathy, reduced contractile force, delayed relaxation and potassium sensitive skeletal muscle weakness. A switch from a mixture of glycolytic and oxidative muscle fibers to an increased number of oxidative fibers is observed in multiple muscle types. The donating investigator reports that the Scn4a^tm1.1Ljh allele (neo out) has the same phenotype as the Scn4a^tm1Ljh allele (neo in) reported in Hayward et al, 2009. This mutant strain may be useful in studies of myotonia, vacuolar myopathy and hyperkalemic periodic paralysis (HyperKPP).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector was designed to create a missense substitution corresponding to the human HyperKPP mutation in the murine Scn4a cDNA sequence. The mutation changes a methionine to a valine at amino acid position 1592 in exon 24 (M1592V). A loxP-flanked PGKneo cassette was also inserted within intron 23. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The neomycin cassette was removed by transient transfection with a Cre recombinase expressing plasmid leaving a single loxP site downstream of exon 23. The resulting chimeric animals were crossed to C57BL/6 mice for several generations and then to FVB for a minimum of 10 generations.

Control Information

	Control
	Wild-type from the colony
	001800 FVB/NJ
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Hyperkalemic Periodic Paralysis; HYPP

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Hypokalemic Periodic Paralysis, Type 2; HOKPP2   (SCN4A) Myasthenic Syndrome, Congenital, Acetazolamide-Responsive   (SCN4A) Myotonia, Potassium-Aggravated   (SCN4A) Paramyotonia Congenita of Von Eulenburg; PMC   (SCN4A)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Scn4a^tm1.1Ljh/Scn4a⁺

        B6.129S4-Scn4a^tm1.1Ljh

• muscle phenotype
• abnormal muscle physiology   (MGI Ref ID J:135831)
• • impaired muscle relaxation   (MGI Ref ID J:135831)
  • impaired skeletal muscle contractility   (MGI Ref ID J:135831)
  • increased muscle relaxation   (MGI Ref ID J:135831)
  • muscle fatigue   (MGI Ref ID J:135831)
  • muscle weakness   (MGI Ref ID J:135831)
  • myopathy   (MGI Ref ID J:135831)
• abnormal skeletal muscle fiber morphology
  • phenotype is stated to be identical to that of Scn4a^tm1Ljh heterozygotes, however, no data is presented in J:135831   (MGI Ref ID J:135831)
• • increased variability of skeletal muscle fiber size   (MGI Ref ID J:135831)

Scn4a^tm1.1Ljh/Scn4a^tm1.1Ljh

        B6.129S4-Scn4a^tm1.1Ljh

• mortality/aging
• decreased survivor rate   (MGI Ref ID J:135831)
• partial perinatal lethality
  • phenotype is stated to be identical to that of Scn4a^tm1Ljh homozygotes, however, no data is presented in J:135831   (MGI Ref ID J:135831)
• muscle phenotype
• abnormal skeletal muscle fiber morphology   (MGI Ref ID J:135831)
• • increased variability of skeletal muscle fiber size   (MGI Ref ID J:135831)
• muscle weakness   (MGI Ref ID J:135831)
• myopathy   (MGI Ref ID J:135831)
• skeletal muscle atrophy   (MGI Ref ID J:135831)
• behavior/neurological phenotype
• limb grasping   (MGI Ref ID J:135831)
• growth/size phenotype
• decreased body weight   (MGI Ref ID J:135831)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cell Biology Research
Channel and Transporter Defects
      sodium
Signal Transduction

Neurobiology Research
Neuromuscular Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Scn4atm1.1Ljh
Allele Name		targeted mutation 1.1, Lawrence J Hayward
Allele Type		Targeted (knock-in)
Common Name(s)		SCN4aM1592V;
Mutation Made By		Lawrence Hayward,   University of Massachusetts Medical School
Strain of Origin		129S4/SvJae
Promoter		Scn4a, sodium channel, voltage-gated, type IV, alpha, mouse, laboratory
Molecular Note		The targeting vector inserts a missense substitution changing a methionine to a valine at amino acid position 1592 (M1592V) in exon 24 and a loxP flanked neo cassette in intron 23. The neo cassette is removed by transient infection with a Cre recombinaseexpressing plasmid leaving a single loxP site downstream of exon 23. [MGI Ref ID J:135831] [MGI Ref ID J:153497]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Scn4a^tm1.1Ljh related

Hayward L. 2009. Creation of the M1592V mutation in Scn4a MGI Direct Data Submission :.  [MGI Ref ID J:153497]

Hayward LJ; Kim JS; Lee MY; Zhou H; Kim JW; Misra K; Salajegheh M; Wu FF; Matsuda C; Reid V; Cros D; Hoffman EP; Renaud JM; Cannon SC; Brown RH Jr. 2008. Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness. J Clin Invest 118(4):1437-49. [PubMed: 18317596]  [MGI Ref ID J:135831]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation die by two months of age.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
	001800 FVB/NJ
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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