Mammalian Genome

, Volume 23, Issue 1–2, pp 85–108 | Cite as

Canine models of Duchenne muscular dystrophy and their use in therapeutic strategies

  • Joe N. Kornegay
  • Janet R. Bogan
  • Daniel J. Bogan
  • Martin K. Childers
  • Juan Li
  • Peter Nghiem
  • David A. Detwiler
  • C. Aaron Larsen
  • Robert W. Grange
  • Ratna K. Bhavaraju-Sanka
  • Sandra Tou
  • Bruce P. Keene
  • James F. HowardJr.
  • Jiahui Wang
  • Zheng Fan
  • Scott J. Schatzberg
  • Martin A. Styner
  • Kevin M. Flanigan
  • Xiao Xiao
  • Eric P. Hoffman
Article

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder in which the loss of dystrophin causes progressive degeneration of skeletal and cardiac muscle. Potential therapies that carry substantial risk, such as gene- and cell-based approaches, must first be tested in animal models, notably the mdx mouse and several dystrophin-deficient breeds of dogs, including golden retriever muscular dystrophy (GRMD). Affected dogs have a more severe phenotype, in keeping with that of DMD, so may better predict disease pathogenesis and treatment efficacy. Various phenotypic tests have been developed to characterize disease progression in the GRMD model. These biomarkers range from measures of strength and joint contractures to magnetic resonance imaging. Some of these tests are routinely used in clinical veterinary practice, while others require specialized equipment and expertise. By comparing serial measurements from treated and untreated groups, one can document improvement or delayed progression of disease. Potential treatments for DMD may be broadly categorized as molecular, cellular, or pharmacologic. The GRMD model has increasingly been used to assess efficacy of a range of these therapies. A number of these studies have provided largely general proof-of-concept for the treatment under study. Others have demonstrated efficacy using the biomarkers discussed. Importantly, just as symptoms in DMD vary among patients, GRMD dogs display remarkable phenotypic variation. Though confounding statistical analysis in preclinical trials, this variation offers insight regarding the role that modifier genes play in disease pathogenesis. By correlating functional and mRNA profiling results, gene targets for therapy development can be identified.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Joe N. Kornegay
    • 1
    • 2
    • 3
    • 4
  • Janet R. Bogan
    • 1
    • 3
    • 4
  • Daniel J. Bogan
    • 1
    • 3
    • 4
  • Martin K. Childers
    • 6
  • Juan Li
    • 4
    • 5
  • Peter Nghiem
    • 7
  • David A. Detwiler
    • 1
  • C. Aaron Larsen
    • 8
  • Robert W. Grange
    • 9
  • Ratna K. Bhavaraju-Sanka
    • 2
    • 4
    • 15
  • Sandra Tou
    • 10
  • Bruce P. Keene
    • 10
  • James F. HowardJr.
    • 2
    • 4
  • Jiahui Wang
    • 11
  • Zheng Fan
    • 2
    • 4
  • Scott J. Schatzberg
    • 12
  • Martin A. Styner
    • 13
  • Kevin M. Flanigan
    • 14
  • Xiao Xiao
    • 3
    • 4
    • 5
  • Eric P. Hoffman
    • 7
  1. 1.Department of Pathology and Laboratory MedicineUniversity of North Carolina-Chapel HillChapel HillUSA
  2. 2.Department of NeurologyUniversity of North Carolina-Chapel HillChapel HillUSA
  3. 3.The Gene Therapy CenterUniversity of North Carolina-Chapel HillChapel HillUSA
  4. 4.School of Medicine, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research CenterUniversity of North Carolina-Chapel HillChapel HillUSA
  5. 5.Eshelman School of PharmacyUniversity of North Carolina-Chapel HillChapel HillUSA
  6. 6.Department of Neurology, Institute for Regenerative MedicineWake Forest UniversityWinston-SalemUSA
  7. 7.Department of Integrative Systems Biology, George Washington University School of Medicine, and Research Center for Genetic MedicineChildren’s National Medical CenterWashingtonUSA
  8. 8.Department of Human GeneticsUniversity of UtahSalt Lake CityUSA
  9. 9.Department of Human Nutrition, Foods, and ExerciseVirginia Tech UniversityBlacksburgUSA
  10. 10.Department of Clinical Sciences, College of Veterinary MedicineNorth Carolina State UniversityRaleighUSA
  11. 11.Department of PsychiatryUniversity of North Carolina-Chapel HillChapel HillUSA
  12. 12.Veterinary Emergency and Specialty Center of Santa FeSanta FeUSA
  13. 13.Departments of Computer Science and PsychiatryUniversity of North Carolina-Chapel HillChapel HillUSA
  14. 14.Nationwide Children’s Hospital, Center for Gene TherapyColumbusUSA
  15. 15.Department of NeurologyUniversity of Texas Health Sciences Center, Medical Arts and Research Center (MARC)San AntonioUSA

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