Overview

Also Known As:nmf5

These mice carry an ENU-induced mutation shown to be a new allele of Scn8a and characterized by bilateral hind limb paralysis and early mortality.

The Jackson Laboratory cannot guarantee that cryorecovery of strains from the discontinued NIH-funded Neuroscience Mutagenesis Facility (NMF) will be successful or that the anticipated phenotype or genotype will be obtained. The cryorecovery fee for this effort will not be refunded or prorated if the recovery is unsuccessful or is in any way unsatisfactory. Genotyping will be the responsibility of the Purchaser.

Genetic overview

Genetic Background	Generation

Scn8a^5J

Allele Type	Gene Symbol	Gene Name
Chemically induced (ENU)	Scn8a	sodium channel, voltage-gated, type VIII, alpha

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Research Applications

Sensorineural Research
Neurobiology Research
Cell Biology Research
Developmental Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice develop bilateral hind limb paralysis between 14-22 days (average onset 16.9 +/- 2.1 days) followed by death between 3-4 weeks of age. Mutants of either gender have been produced.

A complementation test between NMF5 and C3HeB/FeJ-Scn8^med-J (JR#3798) revealed that the motor phenotype of NMF5 represents a new allele of Scn8a, which encodes a type VIII voltage-gated sodium channel alpha polypeptide. Affected mice were found in each of 3 litters from heterozygote matings (NMF5 x Scn8^med-J). Of the 25 mice born, 28% were affected (4/8, 1/9, 2/8, litters 1-3, respectively). Additional complementation tests showed NMF5 to be an allele of NMF58, and recent sequencing data confirmed the allelic relationship of NMF58 and Scn8a, and therefore of NMF5 and Scn8a (Mammalian Genome, 15,4, 2004).

However, we note that the retinal phenotype detected in NMF5 has not been reported for any Scn8a allele. To determine whether the retinal phenotype was caused by a closely-linked but independent recessive mutation, we attempted to separate the two mutations by genetic recombinantion. Nineteen F2 intercross progeny from C57BL/6J-Scn8a^nmf5 and A.B6-Tyr⁺ mice were genotyped for Scn8a and two flanking markers, D15Mit43 and D15Mit246, to detect mice carrying recombinant chromosomes in the Scn8a region. Individual recombinants were subsequently analyzed histologically. Although the two phenotypes were concordant in an Scn8a^nmf5/+ mouse carrying a recombination event between D15Mit43 and Scn8a, the retinal layer defect was detected in a mouse carrying a recombination event between Scn8a (heterozygous) and the telomeric marker D15Mit246 (homozygous B6-Scn8a^nmf5-like). These data suggest that the retinal phenotype is caused by a recessive mutation that maps approximately 3.0cM telomeric to Scn8a.

Standard pathology work-up on 6 mutants and 2 unaffected mice (12-40 days of age) showed no apparent defects in PNS or muscle. The ventricles of the brain were enlarged; mild hydrocephalus was observed in 7 of 8 mice examined. A paucity of granule cells was observed in small areas of the cerebellum. Additional muscle histology showed no evidence of atrophy, regeneration or abnormalities in the neuromuscular junction. The outer layer of the retina was thin (normal retina), consisting of 6-7 rather than the expected 11 cell layers in all 8 mice.

Homozygotes are not viable so that a colony has to be maintained through heterozygote matings and ovarian transplants.

Development

This phenotypic deviant was generated by ethylnitrosourea (ENU) mutagenesis in C57BL/6J males (Stock No. 000664), in the Neuroscience Mutagenesis facility at The Jackson Laboratory. Mutagenized males were crossed to C57BL/6J females; G3 descendants of the mutagenized males were selected for neurological impairment.

Control Suggestions

untyped littermate of mutant homozygote

Additional Information

Considerations for Choosing Controls

Genetics

Scn8a^5J

Allele Symbol: Scn8a^5J

Allele Name	5 Jackson
Allele Type	Chemically induced (ENU)
Allele Synonym(s)	neuroscience mutagenesis facility, 5; NMF5; Scn8a^nmf5
Gene Symbol and Name	Scn8a, sodium channel, voltage-gated, type VIII, alpha
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	15
Molecular Note	This phenotypic mutant was identified in an ENU mutagenesis screen. A complementation test between nmf5 and C3HeB/FeJ-Scn8a^med-J revealed that nmf5 is a new allele of Scn8a. Molecular sequence analysis revealed that an A-to-T transversion mutation had occurred that is predicted to change the amino acid isoleucine 1392 to phenylalanine in the encoded protein. This conserved residue is within the S5-S6 pore loop of transmembrane domain 3.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Sensorineural Research
- Retinal Degeneration

Genotype: Scn8a^5J related

Neurobiology Research
- Neuroscience Mutagenesis Facility Strain
- Channel and Transporter Defects
  - sodium
- Neuromuscular defects
- Ataxia (Movement) Defects
Cell Biology Research
- Channel and Transporter Defects
Developmental Biology Research
- Skeletal Defects
  - hydrocephaly

Mammalian Phenotype Terms by Genotype

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

Genotype: Scn8a^5J/Scn8a^5J
C57BL/6J-Scn8a<5J>/J

behavior/neurological phenotype

hindlimb paralysis
- loss of the use of hindlimbs bilaterally is evident between 14-22 days
- standard pathological workup on 6 mutants and 2 unaffected mice (12-40 days of age) showed no apparent defects in PNS or muscle; additional muscle histology showed no evidence of atrophy, regeneration or abnormalities in the neuromuscular junction

mortality/aging

postnatal lethality, complete penetrance
- Homozygotes die between 3 and 4 weeks of age

nervous system phenotype

abnormal brain morphology

decreased cerebellar granule cell number
- a paucity of granule cells was observed in small areas of the cerebellum

enlarged brain ventricles
- ventricles were enlarged

hydrocephaly
- mild hydrocephalus was noted in 7 of 8 mutant mice examined

References

Additional - Scn8a^5J related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Appearance
- black
  Related Genotype: a/a
Citation
When using the nmf5 mouse strain in a publication, please cite the originating article(s) and include JAX stock #004105 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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Unknown for Scn8a<5J>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

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JAX® Mice, Products & Services Conditions of Use

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Also Known As:nmf5

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Scn8a5J

Allele Symbol: Scn8a5J

Disease Terms

Research Areas By Phenotype

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

Genotype: Scn8a5J related

Mammalian Phenotype Terms by Genotype

Genotype: Scn8a5J/Scn8a5JC57BL/6J-Scn8a<5J>/J

behavior/neurological phenotype

mortality/aging

nervous system phenotype

References

Additional - Scn8a5J related

Genotyping Protocols

Appearance

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

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

Scn8a^5J

Allele Symbol: Scn8a^5J

Genotype: Scn8a^5J related

Genotype: Scn8a^5J/Scn8a^5J
C57BL/6J-Scn8a<5J>/J

Additional - Scn8a^5J related