Olby N J, Sharp N J, Anderson L V, Kunkel L M, Bönnemann C G
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Neuromuscul Disord. 2001 Jan;11(1):41-9. doi: 10.1016/s0960-8966(00)00166-8.
Labrador retrievers suffer from an autosomal recessive muscular dystrophy of unknown aetiology. Dogs affected with this disease develop generalized weakness associated with severe, generalized skeletal muscle atrophy and mild elevations in creatine kinase in the first few months of life. The severity of signs tends to progress over the first year of life but can vary from mild exercise intolerance to non-ambulatory tetraparesis. Beyond 1 year of age, the signs usually stabilize and although muscle mass does not increase, affected dogs' strength may improve slightly. The pathological changes present on muscle biopsy include marked variation in muscle fibre size with hypertrophied and round atrophied fibres present. There is an increased number of fibres with central nuclei and split fibres can be seen. It has been suggested that the disorder is a model for limb-girdle muscular dystrophy. In recent years, mutations in genes encoding the proteolytic enzyme, calpain 3, a novel protein named dysferlin, and components of the dystrophin-glycoprotein complex have been identified as causes of autosomal recessive limb-girdle muscular dystrophy. We have evaluated these proteins in normal dogs and in three Labrador retrievers with autosomal recessive muscular dystrophy using immunohistochemistry and Western blot analysis on frozen skeletal muscle. The results demonstrate that dystrophin, the sarcoglycans, alpha-actinin, dysferlin and calpain 3 are present in the normal and affected dogs. We conclude that this autosomal recessive muscular dystrophy is not due to a deficiency of alpha-actinin, or any of the known autosomal recessive limb-girdle muscular dystrophy proteins, although we cannot rule out a malfunction of any of these proteins.
拉布拉多寻回犬患有病因不明的常染色体隐性遗传性肌肉萎缩症。患此病的犬在出生后的头几个月会出现全身无力，伴有严重的全身性骨骼肌萎缩以及肌酸激酶轻度升高。症状的严重程度在出生后的第一年往往会逐渐加重，但可能从轻度运动不耐受到非行走性四肢轻瘫不等。超过1岁后，症状通常会稳定下来，尽管肌肉量不会增加，但患病犬的力量可能会稍有改善。肌肉活检显示的病理变化包括肌纤维大小显著不同，既有肥大的纤维，也有圆形萎缩的纤维。有中央核的纤维数量增加，还可见到分裂纤维。有人认为这种疾病是肢带型肌营养不良的一种模型。近年来，已确定编码蛋白水解酶钙蛋白酶3、一种名为dysferlin的新蛋白以及肌营养不良蛋白-糖蛋白复合物成分的基因突变是常染色体隐性肢带型肌营养不良的病因。我们利用免疫组织化学和对冷冻骨骼肌的蛋白质印迹分析，对正常犬和三只患有常染色体隐性遗传性肌肉萎缩症的拉布拉多寻回犬的这些蛋白质进行了评估。结果表明，肌营养不良蛋白、肌聚糖、α-辅肌动蛋白、dysferlin和钙蛋白酶3在正常犬和患病犬中均有表达。我们得出结论，这种常染色体隐性遗传性肌肉萎缩症并非由α-辅肌动蛋白或任何已知的常染色体隐性肢带型肌营养不良蛋白缺乏所致，尽管我们不能排除这些蛋白中的任何一种存在功能异常。
