Mice homozygous/hemizygous for the spontaneous Dmdmdx 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.
Dongsheng Duan, University of Missouri
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Spontaneous | Dmd | dystrophin, muscular dystrophy |
Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
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.
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-Dmdmdx/J for more than 9 generations.
Expressed Gene | DMD, dystrophin, human |
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Site of Expression |
Allele Name | X linked muscular dystrophy |
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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. |
Allele Name | transgene insertion 326, Dongsheng Duan |
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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. |
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.
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.
Facility Barrier Level Descriptions
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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