Characterization of Australian Labradoodle dystrophinopathy
| Autor: | Stephanie M. Shrader, Thomas S. Denney, Bruce F. Smith, SeungWoo Jung |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Duchenne muscular dystrophy Cardiomyopathy Exercise intolerance Dystrophin 03 medical and health sciences Dogs 0302 clinical medicine Cardiac magnetic resonance imaging Internal medicine medicine Animals Dog Diseases Muscle Skeletal Myopathy Genetics (clinical) biology medicine.diagnostic_test business.industry Australia Cardiac muscle Skeletal muscle Muscular Dystrophy Animal medicine.disease 030104 developmental biology medicine.anatomical_structure Neurology Mutation Pediatrics Perinatology and Child Health Cardiology biology.protein Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Neuromuscular Disorders. 28:927-937 |
| ISSN: | 0960-8966 |
| Popis: | In humans, dystrophin mutations cause the X-linked recessive disorder known as Duchenne muscular dystrophy (DMD). These mutations result in skeletal and cardiac muscle damage with mortality increasingly associated with cardiomyopathy. We have identified a novel dystrophin mutation in exon 21 in a line of Australian Labradoodles; affected dogs develop progressive clinical signs including poor weight gain and weight loss, gait abnormalities, exercise intolerance, skeletal muscle atrophy, macroglossa, ptyalism, dysphagia, kyphosis, and a plantigrade stance. Echocardiographic abnormalities include hyperechoic foci in the left ventricular papillary muscles, septal hypokinesis, and decreased left ventricular systolic and diastolic volume and internal diameter. Holter recordings found a Mobitz type II second-degree atrioventricular (AV) block in one affected dog. Analysis of phosphocreatine-to-ATP ratios (PCr/ATP) (obtained via cardiac magnetic resonance imaging and spectroscopy evaluation), found no statistically significant difference in the mean PCr/ATP between groups. Histopathologic skeletal muscle changes included fibrofatty infiltration, myocyte degeneration, necrosis, and regeneration, lymphohistiocytic inflammation, and mineralization; cardiac changes were limited to a focal area of mineralization adjacent to the sinoatrial node in the dog with a second-degree AV block. Due to rapidly progressive clinical signs, a severe phenotype, and potential for cardiac involvement, Australian Labradoodle dystrophinopathy may be a useful model to further study DMD pathogenesis. |
| Databáze: | OpenAIRE |
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