September 4, 2012

Duchenne Muscular Dystrophy Mouse Models at JAX

Neuromuscular degenerative diseases affect millions of Americans. We recently published articles illustrating how some of our mice are being used to find therapies and/or cures for amyothrophic lateral sclerosis and spinal muscular atrophy. In this article, we feature several mouse models that can be used to research Duchenne muscular dystryphy (DMD). We also refer you to other resources we offer for DMD research and to DMD research conducted with our mice.

Duchenne Muscular Dystrophy

DMD is a rare, sex-linked, recessive, early onset disease that generally affects children between two and six years old. One of nine types of muscular dystrophy, DMD is caused by a mutant X-linked dystrophin (DMD) gene. The gene encodes dystrophin, a cytoskeletal protein that mediates muscle contraction. Initially, muscles in the hip, pelvic, thigh, and shoulder weaken. People with DMD rarely live past 30 (Muscular Dystrophy Association).

JAX DMD mouse models

Our more popular DMD mouse models are those with the Dmdmdx allele, a spontaneous mutation that introduces a termination codon in the Dmd gene and prevents dystrophin expression. Our standard Dmdmdx mutants and those under development are described below:

C57BL/10ScSn-Dmdmdx/J (001801)
lab mouse, stock number 001801

  • Harbors the spontaneous Dmdmdx mutation
  • Like people with DMD, does not express dystrophin
  • Routinely used as a DMD model, though its myopathology is much less severe than that in humans
  • Homozygous females and hemizygous males live for up to two years
  • Muscles are normal at birth, but muscle necrosis and weakness are observable by about three weeks

STOCK Utrntm1Ked Dmdmdx/J (014563)

  • Harbors a knockout allele of the utrophin gene (Utrntm1Ked) and the Dmdmdx allele
  • Females homozygous for both alleles and males homozygous for Utrntm1Ked and hemizygous for Dmdmdx have a more severe phenotype than mice with the single Dmdmdx allele (clinical symptoms as early as 4 weeks and die by 20 weeks)
  • Dystrophy phenotypes include growth retardation, weight loss, joint contractures, reduced mobility, slack posture, waddling gait, diaphragm necrosis, abnormal breathing, kyphosis, dystrophy of extraocular muscles, abnormal electrocardiograms, and infertility

STOCK Utrntm1Jrs Dmdmdx/J (016622)

  • Harbors a different knockout allele of the utrophin gene (Utrntm1Jrs) than the one above
  • Females homozygous for both alleles and males homozygous for Utrntm1Jrs and hemizygous for Dmdmdx live 4-20 weeks (only half survive beyond 8 weeks)
  • Dystrophy phenotypes include delayed growth, small size, progressive skeletal muscle degeneration, waddling gait, progressive fibrosis throughout the heart, abnormal echocardiography, and kyphosis

B10.Cg-Cmahtm1Avrk Dmdmdx/PtmJ (017929)

  • Homozygous for the Cmahtm1Avrk allele and either homozygous (females) or hemizygous (males) for Dmdmdx
  • The Cmahtm1Avrk allele abolishes CMAH expression, preventing biosynthesis of N-glycolylneuraminic acid (Neu5Gc) from all cells and mimicking human CMAH deficiency
  • Onset of dystrophy is earlier, disease progresses faster, and major DMD phenotypes are more severe than in single mutant Dmdmdx mice
  • Under development; accepting orders; estimated available for sale: January 28, 2013

B10ScSn.Cg-Prkdcscid Dmdmdx/J (018018)

  • “MDX/SCID” mice harbor the Prkdcscid and Dmdmdx alleles
  • DMD phenotypes are partially ameliorated (slower rate of muscle fibrosis, more endurance, and less expression of active TGFB1)
  • DMD phenotypes include necrosis, centrally located nuclei, and characteristic muscle degeneration are still present
  • May be used to transplant human donor cells to evaluate skeletal muscle regeneration
  • Under development; accepting orders; estimated available for sale: January 14, 2013

D2.B10-Dmdmdx/J (013141)

  • Produced by backcrossing C57BL/10ScSn-Dmdmdx/J mice (001801) to DBA/2J (D2, 000671)
  • We are informing customers of any unique Dmdmdx phenotypes on the D2 and other backgrounds as they become known (for example, see Fukada et al. 2010)
  • Awaiting transfer from the donor; register interest

A technical difficulty posed by the C57BL/10ScSn-Dmdmdx/J (001801) strain is the frequency of spontaneous reversion of the mdx mutation, complicating the analysis of gene and cell therapies. The following four strains have unique mutations (due to location) that mitigate this problem and are more amenable to gene- and cell-based therapeutic evaluation:

  • B6Ros.Cg-Dmdmdx-4Cv/J  (002378)
  • B6Ros.Cg-Dmdmdx-2Cv/J  (002388)
  • B6Ros.Cg-Dmdmdx-3Cv/J (002377)
  • B6Ros.Cg-Dmdmdx-5Cv/J (002379)

For more details about any of our DMD models, simply insert the model’s stock number into the appropriate box in the JAX® Mice query form and click!

JAX resources for muscular dystrophy research