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

Content Provider	Springer Nature Link
Author	Kornegay, Joe N. Bogan, Janet R. Bogan, Daniel J. Childers, Martin K. Li, Juan Nghiem, Peter Detwiler, David A. Larsen, C. Aaron Grange, Robert W. Bhavaraju Sanka, Ratna K. Tou, Sandra Keene, Bruce P. Howard, James F. Wang, Jiahui Fan, Zheng Schatzberg, Scott J. Styner, Martin A. Flanigan, Kevin M. Xiao, Xiao Hoffman, Eric P.
Copyright Year	2012
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.
Starting Page	85
Ending Page	108
Page Count	24
File Format	PDF
ISSN	09388990
Journal	Mammalian Genome
Volume Number	23
Issue Number	1-2
e-ISSN	14321777
Language	English
Publisher	Springer-Verlag
Publisher Date	2012-01-05
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Zoology Cell Biology Anatomy
Content Type	Text
Resource Type	Article
Subject	Genetics

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