Identification of three distinguishable phenotypes in golden retriever muscular dystrophy

Abstract

ABSTRACT. Duchenne muscular dystrophy (DMD) is a human disease characterized by progressive and irreversible skeletal muscle degeneration caused by mutations in genes coding for important muscle proteins. Unfortunately, there is no efficient treatment for this disease; it causes progressive loss of motor and muscular ability until death. The canine model (golden retriever muscular dystrophy) is similar to DMD, showing similar clinical signs. Fifteen dogs were followed from birth and closely observed for clinical signs. Dogs had their disease status confirmed by polymerase chain reaction analysis and genotyping. Clinical observations of musculoskeletal, morphological, gastrointestinal, respiratory, cardiovascular, and renal features allowed us to identify three distinguishable phenotypes in dystrophic dogs: mild (grade I), moderate (grade II) and severe (grade III). These three groups showed no difference in dystrophic alterations of muscle morphology and creatine kinase levels. This information will be useful for therapeutic trials, because DMD also shows significant, inter-and intra-familiar clinical variability. Additionally, being aware of phenotypic differences in this animal model is essential for correct interpretation and understanding of results obtained in pre-clinical trials.

Systemic Delivery of Allogenic Muscle Stem Cells Induces Long-Term Muscle Repair and Clinical Efficacy in Duchenne Muscular Dystrophy Dogs

“…Taking into account that the clinical courses are quite similar inside the mocktreated and the treated dog groups, and are also dramatically distinct between the two groups, the clinical impact determined in the treated GRMD dogs probably cannot be explained alone by the phenotypic variability known among GRMD dogs. 80 A limitation of the present study still resides in the minor size of the dog group. To extrapolate the present results to prospective human trials, a more detailed functional phenotype characterization of treated GRMD dogs will be required to complete the clinical grading that corresponds to a semiquantitative approach.…”

Polymorphisms of three new microsatellite sites of the dystrophin gene

“…The hypothesis of "reading frame" considering the severity of the phenotype depends on whether the mutations affect the reading frame, rather than depending on the size of deletion or duplication fragment (Walmsley et al, 2010). Recently, animal studies provided similar findings (Banks and Chamberlain, 2008;Ambrosio et al, 2009;Walmsley et al, 2010).…”

Golden Retriever Muscular Dystrophy (GRMD) como modelo morfofuncional da reparação tecidual na Distrofia Muscular de Duchenne

“…Ambrosio et al (2009) relatam que, aos quatro meses de vida, já se observa essa mesma hiperflexão do tarso associada ao genuvalgum ou genuvarum. Essa característica da articulação do tarso confere à marcha animal a denominação de plantígrada (THIBAUD et al, 2007).…”

“…Porém, essas evidências anteriores (HOWELL et al, 1997;AMBROSIO et al, 2009) somadas a resultados prévios de medidas passivas da ADM ) e aos achados desta pesquisa, indicam que o tarso sofre um aumento da ADM passiva e ativa, ao longo de tempo nesses animais.…”