James R Mickelson1, Katie M Minor2, Ling T Guo3, Steven G Friedenberg4, Jonah N Cullen4, Amanda Ciavarella5, Lydia E Hambrook5, Karen M Brenner6, Sarah E Helmond7, Stanley L Marks8, G Diane Shelton3. 1. Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, 55113, USA. micke001@umn.edu. 2. Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, 55113, USA. 3. Department of Pathology, School of Medicine, University of California San Diego, La Jolla, CA, 92093-0709, USA. 4. Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN, 55113, USA. 5. Advanced Vetcare, Kensington, Victoria, Australia. 6. Centre for Animal Referral and Emergency, Collingwood, Victoria, Australia. 7. Animal Referral Hospital, Homebush, New South Wales, Australia. 8. Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, USA.
Abstract
BACKGROUND: A cohort of related miniature dachshund dogs with exercise intolerance, stiff gait, dysphagia, myoglobinuria, and markedly elevated serum creatine kinase activities were identified. METHODS: Muscle biopsy histopathology, immunofluorescence microscopy, and western blotting were combined to identify the specific pathologic phenotype of the myopathy, and whole genome SNP array genotype data and whole genome sequencing were combined to determine its genetic basis. RESULTS: Muscle biopsies were dystrophic. Sarcoglycanopathy, a form of limb-girdle muscular dystrophy, was suspected based on immunostaining and western blotting, where α, β, and γ-sarcoglycan were all absent or reduced. Genetic mapping and whole genome sequencing identified a premature stop codon mutation in the sarcoglycan A subunit gene (SGCA). Affected dachshunds were confirmed on several continents. CONCLUSIONS: This first SGCA mutation found in dogs adds to the literature of genetic bases of canine muscular dystrophies and their usefulness as comparative models of human disease.
BACKGROUND: A cohort of related miniature dachshund dogs with exercise intolerance, stiff gait, dysphagia, myoglobinuria, and markedly elevated serum creatine kinase activities were identified. METHODS: Muscle biopsy histopathology, immunofluorescence microscopy, and western blotting were combined to identify the specific pathologic phenotype of the myopathy, and whole genome SNP array genotype data and whole genome sequencing were combined to determine its genetic basis. RESULTS: Muscle biopsies were dystrophic. Sarcoglycanopathy, a form of limb-girdle muscular dystrophy, was suspected based on immunostaining and western blotting, where α, β, and γ-sarcoglycan were all absent or reduced. Genetic mapping and whole genome sequencing identified a premature stop codon mutation in the sarcoglycan A subunit gene (SGCA). Affected dachshunds were confirmed on several continents. CONCLUSIONS: This first SGCA mutation found in dogs adds to the literature of genetic bases of canine muscular dystrophies and their usefulness as comparative models of human disease.
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Authors: Melissa L Cox; Jacquelyn M Evans; Alexander G Davis; Ling T Guo; Jennifer R Levy; Alison N Starr-Moss; Elina Salmela; Marjo K Hytönen; Hannes Lohi; Kevin P Campbell; Leigh Anne Clark; G Diane Shelton Journal: Skelet Muscle Date: 2017-07-11 Impact factor: 4.912
Authors: G Diane Shelton; Katie M Minor; Kefeng Li; Jane C Naviaux; Jon Monk; Lin Wang; Elizabeth Guzik; Ling T Guo; Vito Porcelli; Ruggiero Gorgoglione; Francesco M Lasorsa; Peter J Leegwater; Antonio M Persico; James R Mickelson; Luigi Palmieri; Robert K Naviaux Journal: J Neuromuscul Dis Date: 2019
Authors: G Diane Shelton; Katie M Minor; Ling T Guo; Steven G Friedenberg; Jonah N Cullen; Jeffrey M Hord; David Venzke; Mary E Anderson; Megan Devereaux; Sally J Prouty; Caryl Handelman; Kevin P Campbell; James R Mickelson Journal: Neuromuscul Disord Date: 2021-07-28 Impact factor: 4.296