Overview

Also Known As:mdx Δ R4-23/Δ C

Mice homozygous/hemizygous for the spontaneous Dmd^mdx allele and homozygous for the human micro-dystrophin (Δ R4-23/Δ C) transgene exhibit improved skeletal muscle function and muscle histopathology as compared to mdx mice and may be useful for studying Duchenne muscular dystrophy.

Donating Investigator

Dongsheng Duan, University of Missouri

Genetic overview

Genetic Background	Generation

Dmd^mdx

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

Tg(ACTA1-DMD*)326Dua

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

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Research Applications

Neurobiology Research
Sensorineural Research
Mouse/Human Gene Homologs
Cell Biology Research

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Details

Detailed Description

Duchenne muscular dystrophy (DMD) is a progressive muscular disorder caused by an imbalance between muscle degeneration and regeneration resulting in muscle degeneration, necrosis, accumulation of fat and fibrosis, and insufficient regeneration/loss of myofibers. The genetic cause of DMD are mutations of the dystrophin muscular dystrophy gene (DMD) on the X chromosome. The mdx mutation in mice results in a truncated DMD protein. Homozygous females and hemizygous males develop the myopathic features of DMD; although the myopathology is less severe than the human disease course. The Tg(ACTA1-DMD*)326Dua transgene carries a deletion in the human dystrophin gene of repeat 4 through repeat 23 and the C-terminus (Δ R4-23/Δ C) under the control of the human skeletal alpha 1 actin (ACTA1) promoter. When the transgene is combined with the mdx allele, the donating investigator reports that homozygous mice exhibit restored skeletal muscle function and improved muscle histopathology as compared to mdx mice.

Development

The spontaneous mutation "X chromosome-linked muscular dystrophy" (mdx) 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.). The mdx mutation was identified as a C-to-T transition resulting in a termination codon at position 2983(ENSMUST00000114000 chrX:g.83803333 C>T; p.Q995*) 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].

The transgenic construct contains a full length human dystrophin gene modified by the deletion of repeat 4 through repeat 23 and the C-terminus to generate a micro-dystrophin cDNA (Δ R4-23/Δ C) under the control of the human skeletal alpha 1 actin (ACTA1) promoter. The transgene was microinjected into the pronucleus of fertilized FVB/N mouse eggs. Founder line 326 was established and crossed to C57BL/10ScSn-Dmd^mdx/J for more than 9 generations.

Expression Data

Expressed Gene	DMD, dystrophin, human
Site of Expression

Control Suggestions

000666 C57BL/10SnJ

Additional Information

Considerations for Choosing Controls

Selected References

Li D; Yue Y; Lai Y; Hakim CH; Duan D. 2011. Nitrosative stress elicited by nNOSmicro delocalization inhibits muscle force in dystrophin-null mice. J Pathol 223(1):88-98PubMed: 21125668 MGI: J:167308

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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.

Tg(ACTA1-DMD*)326Dua

Allele Symbol: Tg(ACTA1-DMD*)326Dua

Allele Name	transgene insertion 326, Dongsheng Duan
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	deltaR4-23/deltaC
Gene Symbol and Name	Tg(ACTA1-DMD*)326Dua, transgene insertion 326, Dongsheng Duan
Gene Synonym(s)
Promoter	ACTA1, actin, alpha 1, skeletal muscle, human
Expressed Gene	DMD, dystrophin, human
Strain of Origin	FVB/N
Chromosome	UN
Molecular Note	The transgenic construct contains a full length human dystrophin gene modified by the deletion of repeat 4 through repeat 23 and the C-terminus to generate a micro-dystrophin cDNA (deltaR4-23/deltaC) under the control of the human skeletal alpha 1 actin (ACTA1) promoter.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Neurobiology Research
- Muscular Dystrophy
  - Duchenne type

Genotype: Dmd^mdx related

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

Mammalian Phenotype Terms by Genotype

References

Li D; Yue Y; Lai Y; Hakim CH; Duan D. 2011. Nitrosative stress elicited by nNOSmicro delocalization inhibits muscle force in dystrophin-null mice. J Pathol 223(1):88-98PubMed: 21125668 MGI: J:167308

Additional - Dmd^mdx related

Additional - Tg(ACTA1-DMD*)326Dua related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Tg(ACTA1-DMD*)326Dua
- End Point Analysis:DmdEnd Point
- Standard PCR:Tg(DMD*)#Dua
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, mice carrying the X-linked mdx allele are bred as homozygote female x hemizygote male. Mice homozygous for the transgene are viable and fertile.
- Additional Breeding and Husbandry Support
Citation
When using the mdx Δ R4-23/Δ C mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #41193 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.

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:mdx Δ R4-23/Δ C

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Dmdmdx

Allele Symbol: Dmdmdx

Tg(ACTA1-DMD*)326Dua

Allele Symbol: Tg(ACTA1-DMD*)326Dua

Disease Terms

Research Areas By Phenotype

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

Genotype: Dmdmdx related

Mammalian Phenotype Terms by Genotype

References

Additional - Dmdmdx related

Additional - Tg(ACTA1-DMD*)326Dua 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

Dmd^mdx

Allele Symbol: Dmd^mdx

Genotype: Dmd^mdx related

Additional - Dmd^mdx related