Overview

Also Known As:mdx/utrn -

Mice homozygous for the Utrn^tm1Jrs and Dmd^mdx exhibit an onset of skeletal muscle dystrophy as early as 4 weeks of age and are a model for Duchenne Type Muscular Dystrophy.

Donating Investigator

Suzanne Berry, University of Illinois

Genetic overview

Genetic Background	Generation

Dmd^mdx

Allele Type	Gene Symbol	Gene Name
Spontaneous	Dmd	dystrophin, muscular dystrophy

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Utrn	utrophin

Research Applications

Neurobiology Research
Cardiovascular Research
Research Tools
Sensorineural Research
Mouse/Human Gene Homologs
Cell 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 homozygous for the Utrn^tm1Jrs and Dmd^mdx alleles have a lifespan of 4 to 20 weeks, with only 50% surviving beyond 8 weeks of age. As early as 3 weeks of age homozygotes display growth delays, are smaller than wildtype controls and exhibit skeletal muscle dystrophy with abnormal waddling gait at 4 weeks of age. At 10 weeks of age, double mutants exhibit skeletal muscle degeneration, necrosis and interstitial fibrosis, as well as abnormal echocardiography results. By 15 weeks of age, the double homozygotes develop dilated cardiomyopathy. The double mutants exhibit kyphosis, compromised systolic and diastolic function, progressive fibrosis throughout the heart, cardiomyocyte membrane damage, ventricular cellular necrosis, and disorganized mitochondria and myofibrils in cardiomyocytes.

Development

These double mutant mice were produced by breeding mice carrying the Utrn^tm1Jrs targeted mutation and the Dmd^mdx spontaneous mutation.

To generate the Utrn^tm1Jrs targeted mutation, a targeting vector containing PGK-Neo cassette was used to disrupt an exon encoding the beginning of the cysteine-rich region of the protein. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The mice were maintained on a mixed B6;129 background.

The Dmd^mdx spontaneous mutation arose just prior to 1977 at the Agricultural Research Council's Poultry Research Centre, U.K., in C57BL/10ScSn mice obtained from M. Festing (MRC Laboratory Animals Centre, Carshalton, Surrey, U.K.). Mice carrying the Dmd^mdx allele were imported to The Jackson Laboratory in 1984 by Dr. Thomas Roderick, who received them from Dr. Karen Moore (Department of Genetics, University of California, Berkley). A C-to-T transition occurred at position 2983(ENSMUST00000114000 chrX:g.83803333 C>T; p.Q995*), resulting in a termination codon in place of a glutamine codon codon within exon 23 of the dystrophin muscular dystrophy gene (Dmd) on the X chromosome [note that Sicinski et al., 1989 originally reported termination codon at position 3185].

Control Suggestions

Please Inquire

Additional Information

Considerations for Choosing Controls

Selected References

Chun JL; O'Brien R; Berry SE. 2012. Cardiac dysfunction and pathology in the dystrophin and utrophin-deficient mouse during development of dilated cardiomyopathy. Neuromuscul Disord 22(4):368-79PubMed: 22266080 MGI: J:187876

View All References

Genetics

Dmd^mdx

Allele Symbol: Dmd^mdx

Allele Name	X linked muscular dystrophy
Allele Type	Spontaneous
Allele Synonym(s)	mdx; pke; pyruvate kinase expression
Gene Symbol and Name	Dmd, dystrophin, muscular dystrophy
Gene Synonym(s)
Strain of Origin	C57BL/10ScSn
Chromosome	X
Molecular Note	This mutation arose in 1981 in a C57BL/10ScSn colony at University of Leicester. A C-to-T substitution in the CAA codon in exon 23 (ENSMUST00000114000 chrX:g.83803333C>T; c.2983C>T; p.Q995*) results in a termination codon (TAA) in place of a glutamine codon. This allele is predicted to produce a truncated protein.

Utrn^tm1Jrs

Allele Symbol: Utrn^tm1Jrs

Allele Name	targeted mutation 1, Joshua R Sanes
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	uko; utrn-
Gene Symbol and Name	Utrn, utrophin
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	10
Molecular Note	A neomycin resistance cassette replaced 2.7 kb of sequence including 52 bp of the exon that encodes the beginning of the C-terminal cysteine rich region. RT-PCR analysis demonstrated that a mutant transcript carrying the deletion was made in homozygous and heterozygous mice. Western blot analysis on extracts of muscle or lung tissue derived from homozygous mice confirmed that no detectable protein was expressed from this allele.

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).

Duchenne muscular dystrophy

Research Areas By Phenotype

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

Genotype: Dmd^mdx related

Neurobiology Research
- Muscular Dystrophy
  - Duchenne type
Sensorineural Research
- Cataracts
Mouse/Human Gene Homologs
- muscular dystrophy (Duchenne and Becker)
Cell Biology Research
- Signal Transduction

Cardiovascular Research
- Other
- Heart Abnormalities
Research Tools
- Cardiovascular Research
- Neurobiology Research
Neurobiology Research
- Muscular Dystrophy
  - Duchenne type

Mammalian Phenotype Terms by Genotype

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

Genotype: Dmd^mdx/Dmd^mdx Utrn^tm1Jrs/Utrn^tm1Jrs
involves: 129S1/Sv * 129X1/SvJ * C57BL/10ScSn

behavior/neurological phenotype

abnormal gait
- abnormal waddling gait is seen at 4 weeks of age

growth/size/body region phenotype

postnatal growth retardation
- grow more slowly after 3 weeks of age

decreased body size
- significantly smaller by 4 weeks of age

limbs/digits/tail phenotype

abnormal limb morphology
- severe limb contractures
- exhibit contracted and stiff limbs at 4 weeks of age

mortality/aging

premature death
- die between 4 and 14 weeks of age, with only half surviving beyond 8 weeks
- lifespan is 4-20 weeks

muscle phenotype

cardiomyopathy
- develop moderate to severe cardiomyopathy

dystrophic muscle
- begin to exhibit symptoms of skeletal muscle disease at 4 weeks of age and severity progresses with age
- develop severe skeletal muscle dystrophy

muscle degeneration
- muscle degeneration begins earlier than in single Dmd mutants

myocardium necrosis
- necrosis is most prominent in the epicardial surface of the right ventricle, but is seen throughout both ventricles, however ventricles are not dilated or hypertrophic
- large areas of necrotic myocytes with infiltrating mononuclear cells are present in 5 of 9 mutant hearts examined at 8 to 11 weeks of age

skeletal muscle interstitial fibrosis
- seen by 10 weeks of age

skeletal muscle necrosis
- necrosis begins earlier and persists longer than in single Dmd mutants and leads to fibrosis

muscle weakness
- sternomastoid muscle generates only 40-60% as much tension as controls in response to stimulation of its nerve, indicating weakness

abnormal muscle physiology

abnormal muscle relaxation
- relaxation time of muscle (time from peak force to baseline) is greatly prolonged

nervous system phenotype

abnormal neuromuscular synapse morphology
- distribution of acetylcholine receptors within the synapse branches is abnormal, with a patchy distribution
- exhibit fewer junctional folds in the neuromuscular junction

skeleton phenotype

kyphosis

cardiovascular system phenotype

myocardium necrosis
- large areas of necrotic myocytes with infiltrating mononuclear cells are present in 5 of 9 mutant hearts examined at 8 to 11 weeks of age
- necrosis is most prominent in the epicardial surface of the right ventricle, but is seen throughout both ventricles, however ventricles are not dilated or hypertrophic

cardiomyopathy
- develop moderate to severe cardiomyopathy

cellular phenotype

skeletal muscle necrosis
- necrosis begins earlier and persists longer than in single Dmd mutants and leads to fibrosis

myocardium necrosis
- large areas of necrotic myocytes with infiltrating mononuclear cells are present in 5 of 9 mutant hearts examined at 8 to 11 weeks of age
- necrosis is most prominent in the epicardial surface of the right ventricle, but is seen throughout both ventricles, however ventricles are not dilated or hypertrophic

References

Chun JL; O'Brien R; Berry SE. 2012. Cardiac dysfunction and pathology in the dystrophin and utrophin-deficient mouse during development of dilated cardiomyopathy. Neuromuscul Disord 22(4):368-79PubMed: 22266080 MGI: J:187876

Additional - Dmd^mdx related

Additional - Utrn^tm1Jrs related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- End Point Analysis:DmdEnd Point
- Separated PCR:Utrn
- Standard PCR:Utrn
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, mice carrying the Utrn^tm1Jrs allele alone can be bred as homozygotes.

When maintaining a live colony of mice carrying only the Dmd^mdx allele, female mice homozygous for the Dmd^mdx allele and male mice hemizygous for the Dmd^mdx allele can be bred together.

When maintaining a live colony of mice carrying both mutations, female mice that are heterozygous for Utrn^tm1Jrs, homozygous for Dmd^mdx can be bred to male mice that are hemizygous for Dmd^mdx allele.
- Additional Breeding and Husbandry Support
Citation
When using the mdx/utrn - mouse strain in a publication, please cite the originating article(s) and include JAX stock #016622 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 or wildtype for Utrn<tm1Jrs>, Homozygous females and hemizygous males for Dmd<mdx>

Related Products and Services

Frozen Mouse Embryo	STOCK Utrn<tm1Jrs> Dmd<mdx>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	STOCK Utrn<tm1Jrs> Dmd<mdx>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	STOCK Utrn<tm1Jrs> Dmd<mdx>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	STOCK Utrn<tm1Jrs> Dmd<mdx>/J Frozen Embryo	$3373.50

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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. 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

Also Known As:mdx/utrn -

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Dmdmdx

Allele Symbol: Dmdmdx

Utrntm1Jrs

Allele Symbol: Utrntm1Jrs

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:

Genotype: Dmdmdx related

Mammalian Phenotype Terms by Genotype

Genotype: Dmdmdx/Dmdmdx Utrntm1Jrs/Utrntm1Jrsinvolves: 129S1/Sv * 129X1/SvJ * C57BL/10ScSn

behavior/neurological phenotype

growth/size/body region phenotype

limbs/digits/tail phenotype

mortality/aging

muscle phenotype

nervous system phenotype

skeleton phenotype

cardiovascular system phenotype

cellular phenotype

References

Additional - Dmdmdx related

Additional - Utrntm1Jrs 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

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Dmd^mdx

Allele Symbol: Dmd^mdx

Utrn^tm1Jrs

Allele Symbol: Utrn^tm1Jrs

Genotype: Dmd^mdx related

Genotype: Dmd^mdx/Dmd^mdx Utrn^tm1Jrs/Utrn^tm1Jrs
involves: 129S1/Sv * 129X1/SvJ * C57BL/10ScSn

Additional - Dmd^mdx related

Additional - Utrn^tm1Jrs related