These spontaneous Dmdmdx mutant mice do not express dystrophin and may be useful for studying Duchenne muscular dystrophy.
Dongsheng Duan, University of Missouri
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 Dmdmdx mutation in mice has a termination codon in exon 23 that is predicted to result in a truncated protein. Heterozygous females are viable and fertile with no gross phenotypic abnormalities. Homozygous females and hemizygous males are viable and fertile with myopathic features of DMD; although the myopathology is both less severe than the human disease course and variable by mouse strain genetic background.
The donating investigator indicates that mice on the C57BL/6 background exhibit the classic pathology and muscle force reduction observed in the original C57BL/10 background. The muscle pathology includes active fiber necrosis, cellular infiltration, a wide range of fiber sizes, and numerous centrally nucleated regenerating fibers.
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]. Dr. Duan from the University of Missouri introgressed the Dmdmdx allele from C57BL/10ScSn-Dmdmdx/J to the C57BL/6J inbred strain. The backcross number in 2015 is N7.
|Allele Name||X linked muscular dystrophy|
|Allele Synonym(s)||mdx; pke; pyruvate kinase expression|
|Gene Symbol and Name||Dmd, dystrophin, muscular dystrophy|
|Strain of Origin||C57BL/10ScSn|
|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.|
While maintaining a live colony, mice carrying this X-linked mutation are bred as homozygote female x hemizygote male.
When using the mdx/BL6 mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #41196 in your Materials and Methods section.