Sarcoglycan A mutation in miniature dachshund dogs causes limb-girdle muscular dystrophy 2D.

IF 5.3 2区医学 Q2 CELL BIOLOGY

Skeletal Muscle Pub Date : 2021-01-07 DOI:10.1186/s13395-020-00257-y

James R Mickelson, Katie M Minor, Ling T Guo, Steven G Friedenberg, Jonah N Cullen, Amanda Ciavarella, Lydia E Hambrook, Karen M Brenner, Sarah E Helmond, Stanley L Marks, G Diane Shelton

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引用次数: 8

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.

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迷你腊肠犬的肌聚糖A突变会导致四肢带状肌肉萎缩症。

背景:一组相关的小型腊肠犬出现运动不耐受、步态僵硬、吞咽困难、肌红蛋白尿和血清肌酸激酶活性明显升高。方法:结合肌肉活检组织病理学、免疫荧光显微镜和western blotting鉴定肌病的特定病理表型，结合全基因组SNP阵列基因型数据和全基因组测序确定其遗传基础。结果:肌肉活检呈营养不良。肌糖病是一种肢带肌营养不良症，免疫染色和免疫印迹检测结果显示，α、β和γ-肌糖聚糖均缺失或减少。遗传图谱和全基因组测序鉴定了肌聚糖a亚基基因(SGCA)的过早停止密码子突变。在几个大洲都发现了受感染的腊肠犬。结论:在狗身上发现的第一个SGCA突变增加了犬肌营养不良症的遗传基础及其作为人类疾病比较模型的实用性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Skeletal Muscle CELL BIOLOGY-

CiteScore

9.10

自引率

0.00%

发文量

审稿时长

12 weeks

期刊介绍： The only open access journal in its field, Skeletal Muscle publishes novel, cutting-edge research and technological advancements that investigate the molecular mechanisms underlying the biology of skeletal muscle. Reflecting the breadth of research in this area, the journal welcomes manuscripts about the development, metabolism, the regulation of mass and function, aging, degeneration, dystrophy and regeneration of skeletal muscle, with an emphasis on understanding adult skeletal muscle, its maintenance, and its interactions with non-muscle cell types and regulatory modulators. Main areas of interest include: -differentiation of skeletal muscle- atrophy and hypertrophy of skeletal muscle- aging of skeletal muscle- regeneration and degeneration of skeletal muscle- biology of satellite and satellite-like cells- dystrophic degeneration of skeletal muscle- energy and glucose homeostasis in skeletal muscle- non-dystrophic genetic diseases of skeletal muscle, such as Spinal Muscular Atrophy and myopathies- maintenance of neuromuscular junctions- roles of ryanodine receptors and calcium signaling in skeletal muscle- roles of nuclear receptors in skeletal muscle- roles of GPCRs and GPCR signaling in skeletal muscle- other relevant aspects of skeletal muscle biology. In addition, articles on translational clinical studies that address molecular and cellular mechanisms of skeletal muscle will be published. Case reports are also encouraged for submission. Skeletal Muscle reflects the breadth of research on skeletal muscle and bridges gaps between diverse areas of science for example cardiac cell biology and neurobiology, which share common features with respect to cell differentiation, excitatory membranes, cell-cell communication, and maintenance. Suitable articles are model and mechanism-driven, and apply statistical principles where appropriate; purely descriptive studies are of lesser interest.

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