Duchenne muscular dystrophy

One of nine types of muscular dystrophy, DMD is a sexlinked recessive disease characterized by an absence of dystrophin, a protein that helps keep muscle cells intact. It is an early onset disease, generally affecting children when they are two to six years old. Initially, hip, pelvic, thigh, and shoulder muscles weaken, and eventually all muscles, including the heart and breathing muscles, weaken. Affected people rarely live past 30.

JAX® Mice Models

C57BL/10ScSn-Dmdmdx/J

Stock Number 001801

Like people who suffer from DMD, the Dmdmdx mutants do not express dystrophin and therefore have been routinely used as models of the disease, even though the resultant myopathology is much less severe than it is in humans. The mdx mutation of Dmd is recessive, and heterozygous females are visually indistinguishable from wild–type mice. Females homozygous and males hemizygous for the Dmdmdx allele may survive up to two years. Muscle from Dmdmdx mutants is histologically normal early in postnatal development, but muscle necrosis and some visible muscle weakness develops when they are around three weeks old.

References

Bulfield G, Siller WG, Wight PA, Moore KJ. 1984. X chromosome-linked muscular dystrophy (mdx) in the mouse. Proc Natl Acad Sci U S A 81:1189-92.

Ryder-Cook AS, Sicinski P, Thomas K, Davies KE, Worton RG, Barnard EA, Darlison MG, Barnard PJ. 1988. Localization of the mdx mutation within the mouse dystrophin gene. EMBO J 7:3017-21.

Sicinski P, Geng Y, Ryder-Cook AS, Barnard EA, Darlison MG, Barnard PJ 1989. The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science 244:1578-80.

B6Ros.Cg-Dmdmdx-2Cv/J

Stock Number 002388

B6Ros.Cg-Dmdmdx-3Cv/J

Stock Number 002377

B6Ros.Cg-Dmdmdx-4Cv/J

Stock Number 002378

B6Ros.Cg-Dmdmdx-5Cv/J

Stock Number 002379

In contrast to other Dmd mutants, which show no dystrophin reactivity, Dmdmdx-3Cv mutants display a faint dystrophin immunofluorescence in skeletal sarcolemma and skeletal muscle. This is similar to a group of human DMD patients. Dmdmdx-3Cv mutants have a low frequency of revertants. The Dmdmdx-4Cv and Dmdmdx-5Cv strains have 10 times fewer revertants than do the Dmdmdx (see above) and Dmdmdx-2Cv strains. These reversion rate differences are not attributable to either genetic background or viral infections, but rather to differences in the location of the point mutation. The large number of revertants in Dmdmdx mutants has complicated the analysis of gene and cell therapies. The four mutants mentioned here are more useful for this purpose. All these strains are also hemizygous for Hprta and Pgk1a (both are on the X chromosome).

Reference

Chapman VM, Miller DR, Armstrong D, Caskey CT. 1989. Recovery of induced mutations for X chromosomelinked muscular dystrophy in mice. Proc Natl Acad Sci U S A 86:1292-6.