...
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis
【24h】

Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis

机译:全基因组关联分析显示犬变性脊髓病中的SOD1突变类似于肌萎缩性侧索硬化

获取原文
获取原文并翻译 | 示例
           

摘要

Canine degenerative myelopathy (DM) is a fatal neurodegenera-tive disease prevalent in several dog breeds. Typically, the initial progressive upper motor neuron spastic and general propriocep-tive ataxia in the pelvic limbs occurs at 8 years of age or older. If euthanasia is delayed, the clinical signs will ascend, causing flaccid tetraparesis and other lower motor neuron signs. DNA samples from 38 DM-affected Pembroke Welsh corgi cases and 17 related clinically normal controls were used for genome-wide association mapping, which produced the strongest associations with markers on CFA31 in a region containing the canine SOD1 gene. SOD1 was considered a regional candidate gene because mutations in human SOD1 can cause amyotrophic lateral sclerosis (ALS), an adult-onset fatal paralytic neurodegenerative disease with both upper and lower motor neuron involvement. The resequencing of SOD1 in normal and affected dogs revealed a G to A transition, resulting in an E40K missense mutation. Homozygosity for the A allele was associated with DM in 5 dog breeds: Pembroke Welsh corgi. Boxer, Rhodesian ridgeback, German Shepherd dog, and Chesapeake Bay retriever. Microscopic examination of spinal cords from affected dogs revealed myelin and axon loss affecting the lateral white matter and neuronal cytoplasmic inclusions that bind anti-super-oxide dismutase 1 antibodies. These inclusions are similar to those seen in spinal cord sections from ALS patients with SOD1 mutations. Our findings identify canine DM to be the first recognized spontaneously occurring animal model for ALS.
机译:犬变性脊髓病(DM)是一种致命的神经变性疾病,在几种犬种中普遍存在。通常,骨盆四肢最初的进行性上运动神经元痉挛和全身本体性共济失调发生在8岁或8岁以上。如果安乐死被延迟,临床体征会上升,导致松弛的四肢轻瘫和其他下运动神经元体征。来自38个受DM感染的彭布罗克威尔士柯基犬病例和17个相关临床正常对照的DNA样品用于全基因组关联图谱绘制,该图谱在包含犬SOD1基因的区域中与CFA31上的标记产生了最强的关联。 SOD1被认为是区域性候选基因,因为人SOD1中的突变可引起肌萎缩性侧索硬化症(ALS),这是一种成人发作的致命性麻痹性神经退行性疾病,上,下运动神经元均受累。在正常和受影响的狗中SOD1的重新测序显示了从G到A的转变,导致E40K错义突变。 A等位基因的纯合性与5个犬种中的DM相关:彭布罗克威尔士柯基犬图片。拳击手,罗得西亚脊背龙,德国牧羊犬和切萨皮克湾猎犬。患犬脊髓的显微镜检查显示髓磷脂和轴突损失影响结合抗超氧化物歧化酶1抗体的外侧白质和神经元胞浆内含物。这些包含物与具有SOD1突变的ALS患者的脊髓切片中观察到的相似。我们的发现确定犬DM是第一个公认的自发性ALS动物模型。

著录项

  • 来源
  • 作者单位

    Departments of Veterinary Pathobiology, University of Missouri, Columbia MO 65211;

    Departments of Veterinary Pathobiology, University of Missouri, Columbia MO 65211;

    Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge MA 02141 Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, Boston MA 02114;

    Departments of Veterinary Pathobiology, University of Missouri, Columbia MO 65211 Departments of Mason Eye Institute, University of Missouri, Columbia MO 65211;

    Departments of Veterinary Pathobiology University of Missouri, Columbia MO 65211;

    Departments of Division of Animal Sciences, University of Missouri, Columbia MO 65211;

    Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge MA 02141;

    Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge MA 02141;

    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Biomedical Center, Box 597, SE-751 24 Uppsala, Sweden;

    Section of Neurology and Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104;

    Department of Clinical Sciences, Tufts University, North Grafton, MA 01536;

    Department of Clinical Sciences, North Carolina State University, Raleigh, NC 27606;

    Department of Pathology, University of California at San Diego, La Jolla, CA 92093;

    Departments of Veterinary Pathobiology University of Missouri, Columbia MO 65211;

    Departments of Veterinary Medicine and Surgery, University of Missouri, Columbia MO 65211;

    Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge MA 02141;

    Departments of Veterinary Medicine and Surgery, University of Missouri, Columbia MO 65211;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号