Overview

These Dysf (dysferlin) knock-out mutant mice develop a slowly progressive muscular dystrophy. This mutant mouse strain represents a model that may be useful in studies of muscle disease and repair.

Donating Investigator

Kevin Campbell, University of Iowa

Genetic overview

Genetic Background	Generation

Dysf^tm1Kcam

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Dysf	dysferlin

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Research Applications

Neurobiology Research
Mouse/Human Gene Homologs

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for this targeted mutation are viable, fertile and show a normal growth rate. Mice develop a slowly progressive muscular dystrophy. By the age of 2 months, a few individual necrotic and centrally nucleated fibers can be detected throughout the muscle; the number increases with age. By 8 months, the muscle develops all of the pathological characteristics of muscular dystrophy (e.g. regenerating fibers, split fibers, muscle necrosis with macrophage infiltration and fat replacement). The severity of the pathology varies in different muscles. Muscle fibers are defective in Ca²⁺-dependent sarcolemma resealing/repair. No protein product from the targeted gene is detected in skeletal muscle microsomes. This mutant mouse strain represents a model that may be useful in studies of muscle disease and repair.

Development

A targeting vector containing a neomycin resistance gene was use to replace a 12 kb region containing the last three coding exons of the gene, including the exons coding for the transmembrane domain. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. This strain was backcrossed to C57BL/6 for seven generations by the donating laboratory.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Bansal D; Miyake K; Vogel SS; Groh S; Chen CC; Williamson R; McNeil PL; Campbell KP. 2003. Defective membrane repair in dysferlin-deficient muscular dystrophy. Nature 423(6936):168-72PubMed: 12736685 MGI: J:83126
Wiktorowicz T; Kinter J; Kobuke K; Campbell KP; Sinnreich M. 2015. Genetic characterization and improved genotyping of the dysferlin-deficient mouse strain Dysf (tm1Kcam). Skelet Muscle 5:32PubMed: 26464793 MGI: J:285288

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Genetics

Dysf^tm1Kcam

Allele Symbol: Dysf^tm1Kcam

Allele Name	targeted mutation 1, Kevin P Campbell
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)
Gene Symbol and Name	Dysf, dysferlin
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	6
Molecular Note	12 kb of sequences at the 3' end of the gene were replaced with a neomycin resistance cassette via homologous recombination. The gene targeting event results in deletion of the last 3 coding exons including the transmembrane domain. Absence of gene expression in homozygous mutant animals was confirmed by Western blot analysis of skeletal muscle microsomes.
Mutations Made By	Kevin Campbell, University of Iowa

Disease/Phenotype

Disease Terms

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).

Research Areas By Phenotype

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

Neurobiology Research
- Muscular Dystrophy
  - Limb-Girdle type
Mouse/Human Gene Homologs
- muscular dystrophy, limb-girdle
  - type 2B

Mammalian Phenotype Terms by Genotype

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

Genotype: Dysf^tm1Kcam/Dysf^tm1Kcam
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

muscle phenotype

centrally nucleated skeletal muscle fibers
- ~10% of all fibers in mutant skeletal muscle are centrally nucleated by 2 months of age, 20% by 4 months of age, and 48% and 65% by 8 and 10 months, respectively

dystrophic muscle
- the % of centrally nucleated fibers increases with age, with a few individual necrotic and centrally nucleated fibers first evident at 2 months of age
- the severity of muscle pathology varies in different skeletal muscles
- homozygotes develop a slowly progressive muscular dystrophy at the level of single muscle fibers, as evidenced by the presence of individual Evans-blue positive fibers
- by 8 months of age, dystrophic skeletal muscle exhibits regenerating fibers, split fibers, and muscle necrosis with macrophage infiltration, and fat replacement

abnormal sarcolemma morphology
- however, minimal sarcolemma damage is detected in mutant muscle after exercise, indicating the presence of a functional dystrophin-glycoprotein complex (DGC) and stable sarcolemma
- plasma membrane disruptions are identified with Evans blue by 8 months of age

skeletal muscle fiber necrosis
- significant skeletal muscle necrosis with macrophage infiltration and fat replacement is evident by 8 months of age

skeletal muscle fibrosis

skeletal muscle necrosis

abnormal muscle regeneration
- unlike wild-type muscle fibres, mutant skeletal muscle fibres are defective in Ca²⁺-dependent sarcolemma resealing, indicating a disruption of the muscle membrane repair machinery
- in response to sarcolemma injuries, mutant skeletal muscle fibers display sub-sarcolemmal vesicle accumulations, whereas wild-type damaged fibers exhibit only dysferlin-enriched membrane patches

increased variability of skeletal muscle fiber size
- at 9 months of age, a significantly greater muscle fiber size variation is noted in mutant skeletal muscle than in wild-type muscle

myositis
- muscle from 8 month, but not 4 month old, mice shows small numbers of infiltrating lymphocytes; both perivascular and endomysial leukocytes are seen

skeletal muscle fiber degeneration
- active skeletal muscle regeneration occurs in response to muscle degeneration, as evidenced by the presence of centrally nucleated skeletal muscle fibers and increased variability in fiber size

cellular phenotype

skeletal muscle necrosis

skeletal muscle fiber necrosis
- significant skeletal muscle necrosis with macrophage infiltration and fat replacement is evident by 8 months of age

homeostasis/metabolism phenotype

increased circulating creatine kinase level
- homozygotes exhibit a several-fold increase in serum creatine kinase levels relative to wild-type mice
- both before and after exercise

immune system phenotype

myositis
- muscle from 8 month, but not 4 month old, mice shows small numbers of infiltrating lymphocytes; both perivascular and endomysial leukocytes are seen

References

Bansal D; Miyake K; Vogel SS; Groh S; Chen CC; Williamson R; McNeil PL; Campbell KP. 2003. Defective membrane repair in dysferlin-deficient muscular dystrophy. Nature 423(6936):168-72PubMed: 12736685 MGI: J:83126
Wiktorowicz T; Kinter J; Kobuke K; Campbell KP; Sinnreich M. 2015. Genetic characterization and improved genotyping of the dysferlin-deficient mouse strain Dysf (tm1Kcam). Skelet Muscle 5:32PubMed: 26464793 MGI: J:285288

Additional - Dysf^tm1Kcam related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Dysfalternate1
- Genotyping resources and troubleshooting
Download the Genotyping Protocol for Dysf^tm1Kcam from Kevin Campbell, University of Iowa.
Breeding Considerations

When maintaining a live colony, homozygotes or heterozygotes may be bred. Malocclusions may occur which require teeth clipping to allow normal eating and drinking.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129-Dysf^tm1Kcam/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #013149 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
> >	Heterozygous for Dysf<tm1Kcam>

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

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Dysftm1Kcam

Allele Symbol: Dysftm1Kcam

Disease Terms

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).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Dysftm1Kcam/Dysftm1Kcaminvolves: 129S1/Sv * 129X1/SvJ * C57BL/6

muscle phenotype

cellular phenotype

homeostasis/metabolism phenotype

immune system phenotype

References

Additional - Dysftm1Kcam related

Genotyping Protocols

Breeding Considerations

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

Additional Use Restrictions Apply

Licensing Information

Dysf^tm1Kcam

Allele Symbol: Dysf^tm1Kcam

Genotype: Dysf^tm1Kcam/Dysf^tm1Kcam
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Additional - Dysf^tm1Kcam related