JAX Notes July 01, 1991

Dmdmdx mutant mice: a model for muscular dystrophy

Dmdmd: An X-Linked Mutation

X-linked muscular dystrophy (mdx) is a mutation in the dystrophin (Dmd) gene as are the human inherited diseases Duchenne and Becker muscular dystrophy. The mdx/mdx mutant, while not a precise mouse model of either human disease, is studied extensively by researchers interested in these two human X-linked muscular dystrophies and in understanding muscle degeneration and regeneration.

The X-linked muscular dystrophy (mdx) mutation was first described by Bulfield et al. as a murine glycolytic mutation with histological myopathy (Bulfield, Siller and Wight 1982; Bulfield, Siller, Wight and Moore, 1984). The recessive mutation was proposed as a possible mouse model for the human Duchenne and Becker X-linked muscular dystrophies. Dr. Thomas H. Roderick imported mdx/mdx mutation mice to The Jackson Laboratory from Dr. Karen Moore in 1984. The strain is designated C57BL/10ScSn-Dmdmdx/J (001801).

Mutant mdx/mdx strain.

Colony maintenance

Dangain and Vrbova showed that the mild non-progressive expression of mdx in affected mice is due to muscle destruction with subsequent regeneration (Dangain and Vrbova,1984). The strain is maintained by mating homozygous (mdx/mdx) females to hemizygous (mdx/Y) males because the mild phenotype produced by mdx makes visual classification of mutants difficult. Controls for the mutants are obtained from the JAX C57BL/10ScSnJ (000476) or C57BL/10SnJ (000666) colonies. Distinction between mutants and controls can be determined by measuring plasma creatine kinase. Mutants show variable but consistent elevation. Histologically, homozygous mutants show reduced dystrophin antibody staining.

Molecular analysis by Sicinski et al. (Sicinski et al. 1989) indicates that the mdx mutation is a single base substitution within an exon of the mouse dystrophin gene and suggests that the murine dystrophin gene is homologous to the human Duchenne muscular dystrophy (DMD) locus.

References

1. Bulfield, G., Siller W.G., Wight PAL. [change (pke), pyruvate kinase expression to X-linked muscular dystrophy, (mdx).] Mouse News Letter 1982; 66:57.

2. Bulfield, G., Siller W.G., Wight PAL, Moore K.J. X-Chromosome-linked muscular dystrophy (mdx) in the mouse. Proc Natl Acad Sci USA 1984; 81:1189-92.

3. Dangain J., Vrbova G. Muscle development in (mdx) mutant mice. Muscle Nerve 1984; 7:700-704.

4. Sicinski P., Geng Y., Ryder-Cook A.S., Barnard E.A., Darlison M.G., Barnard P.J. The molecular basis of muscular dystrophy in the (mdx) mouse. A point mutation. Science 1989; 244:1578-80.