Overview

Also Known As:SCN1A knockout

Mice homozygous for the Scn1a (voltage gated sodium channel) knockout allele exhibit tremors, ataxia, seizures and die by postnatal day 16. Heterozygous mice on the 129S6/SvEvTac background do not exhibit an overt phenotype, however, on the C57BL/6 background mice develop spontaneous seizures and die within weeks. This strain may be useful for genetic analysis of epilepsy and Dravet syndrome.

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Donating Investigator

Jennifer Kearney, Vanderbilt University

Genetic overview

Genetic Background	Generation

Scn1a^tm1Kea

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Scn1a	sodium channel, voltage-gated, type I, alpha

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Research Applications

Developmental Biology Research
Neurobiology Research

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Details

Detailed Description

Scn1a encodes the alpha subunit of a heteromeric complex forming the voltage sensitive sodium channel. Mutations in SCN1A are associated with several epilepsy syndromes including Dravet Syndrome, an infant-onset epileptic encephalopathy. Mice homozygous for this null allele exhibit tremors, ataxia and seizures; death occurs by postnatal day 16. Heterozygous mice on the C57BL/6 background develop spontaneous seizures and die within weeks. On an F1 hybrid (C57BL/6J x 129S6/SvEvTac) background, heterozygotes exhibit an intermediate phenotype including seizures and a 50% lethality by one month of age. On the 129S6/SvEvTac background, mice do not exhibit an overt phenotype; lifespan is normal and no seizures are recorded by EEG monitoring. This strain may be useful for genetic analysis of epilepsy and Dravet syndrome.

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 containing a loxP-flanked PGKneo cassette was used to replace exon 1. The construct was electroporated into 129S6/SvEvTac-derived TL1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to 129S6/SvEvTac mice and maintained as a cross to 129S6/SvEvTac at every generation. Upon arrival, mice were bred to 129S1/SvImJ mice (Stock No. 002448) for at least 1 generation to establish the colony.

Control Suggestions

Approximate Controls

Wild-type from the colony
002448 129S1/SvImJ

Additional Information

Considerations for Choosing Controls

Selected References

Miller AR; Hawkins NA; McCollom CE; Kearney JA. 2014. Mapping genetic modifiers of survival in a mouse model of Dravet syndrome. Genes Brain Behav 13(2):163-72PubMed: 24152123 MGI: J:203040

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Genetics

Scn1a^tm1Kea

Allele Symbol: Scn1a^tm1Kea

Allele Name	targeted mutation 1, Jennifer Kearney
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Scn1a, sodium channel, voltage-gated, type I, alpha
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	2
Molecular Note	A loxP-flanked neomycin resistance cassette replaced the first coding exon. Absence of protein was confirmed by immunoblotting.

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Dravet syndrome

Research Areas By Phenotype

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

Developmental Biology Research
- Postnatal Lethality
  - Homozygous
Neurobiology Research
- Epilepsy

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Scn1a^tm1Kea/Scn1a⁺
(C57BL/6J x 129S6/SvEvTac-Scn1a)F1

behavior/neurological phenotype

seizures
- Background Sensitivity - mice on a background containing C57BL/6J exhibit spontaneous seizures unlike mice on a coisogenic 129S6/SvEvTac background

mortality/aging

premature death
- Background Sensitivity - mice on a background containing C57BL/6J exhibit premature death with 50% of mice dying by 1 month of age unlike mice on a coisogenic 129S6/SvEvTac background

nervous system phenotype

seizures
- Background Sensitivity - mice on a background containing C57BL/6J exhibit spontaneous seizures unlike mice on a coisogenic 129S6/SvEvTac background

The following phenotype relates to a compound genotype created using this strain

Genotype: Scn1a^tm1Kea/Scn1a⁺
129S6/SvEvTac-Scn1a

normal phenotype

no abnormal phenotype detected
- Background Sensitivity - mice on a coisogenic 129S6/SvEvTac background exhibit no overt phenotype and a normal life span unlike mice on a background containing C57BL/6J

References

Miller AR; Hawkins NA; McCollom CE; Kearney JA. 2014. Mapping genetic modifiers of survival in a mouse model of Dravet syndrome. Genes Brain Behav 13(2):163-72PubMed: 24152123 MGI: J:203040

Additional References

Kang SK; Hawkins NA; Kearney JA. 2019. C57BL/6J and C57BL/6N substrains differentially influence phenotype severity in the Scn1a (+/-) mouse model of Dravet syndrome. Epilepsia Open 4(1):164-169PubMed: 30868126 MGI: J:280110

Additional - Scn1a^tm1Kea related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Scn1a-Alternate 1
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation die by postnatal day 16.
- Additional Breeding and Husbandry Support
Citation
When using the SCN1A knockout mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #37107 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Licensing Information

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Also Known As:SCN1A knockout

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Scn1atm1Kea

Allele Symbol: Scn1atm1Kea

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Scn1atm1Kea/Scn1a+(C57BL/6J x 129S6/SvEvTac-Scn1a)F1

behavior/neurological phenotype

mortality/aging

nervous system phenotype

Genotype: Scn1atm1Kea/Scn1a+129S6/SvEvTac-Scn1a

normal phenotype

References

Additional References

Additional - Scn1atm1Kea related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Scn1a^tm1Kea

Allele Symbol: Scn1a^tm1Kea

Genotype: Scn1a^tm1Kea/Scn1a⁺
(C57BL/6J x 129S6/SvEvTac-Scn1a)F1

Genotype: Scn1a^tm1Kea/Scn1a⁺
129S6/SvEvTac-Scn1a

Additional - Scn1a^tm1Kea related