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Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice

机译：DMRT3中的突变影响马的运动和小鼠的脊髓回路功能

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摘要

有些马(尤其是用于轻驾车赛马的美洲“标准rn种马”和全地形冰岛马)能够表演其他马种不rn能表演的步态。所有的马都能行走、小跑、慢rn跑和奔跑，但有些还能“踱步”——行走时两rn条腿全都在身体的同一侧——同时还能(或者rn还能)表演其他新颖的从容步态。对冰岛马所rn做的一项全基因组关联分析，识别出了在rnDMRT3基因中的一个早熟“终止密码子”和能rn够表演其他步态的能力之间的联系。用小鼠进rn行的功能研究表明，Dmrt3表达在一个亚组的rn脊髓神经元中，这些神经元对于控制肢体运动rn的一个协调的运动网络的正常发育非常关键。rn因此，Dmrt3也许在对控制脊椎动物步幅大小rn的脊髓回路进行配置中起一个关键作用。对驯rn化的马来说，DMRT3突变对它们的多样化有rn重大影响，因为若干品种的被改变的步态特征rn显然需要这一突变。本期封面所示为2004年rn在冰岛Hella举行的由纯种冰岛马参加的rn“Landstnot国际马赛”上一匹参赛的马(ArcticrnImages/Corbis)。%Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement1. These networks produce left-right alternation of limbs as well as coordinated activation of flexor and extensor muscles2. Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favourable effect on harness racing performance. Examination of wild-type and Drt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes part in neuronal specification within this subdivision, and is critical for the normal development of a coordinated locomotor network controlling limb movements. Our discovery positions Dmrt3 in a pivotal role for configuring the spinal circuits controlling stride in vertebrates. The DMRT3 mutation has had a major effect on the diversification of the domestic horse, as the altered gait characteristics of a number of breeds apparently require this mutation.
机译：有些马(尤其是用于轻驾车赛马的美洲“标准rn种马”和全地形冰岛马)能够表演其他马种不rn能表演的步态。所有的马都能行走、小跑、慢rn跑和奔跑，但有些还能“踱步”——行走时两rn条腿全都在身体的同一侧——同时还能(或者rn还能)表演其他新颖的从容步态。对冰岛马所rn做的一项全基因组关联分析，识别出了在rnDMRT3基因中的一个早熟“终止密码子”和能rn够表演其他步态的能力之间的联系。用小鼠进rn行的功能研究表明，Dmrt3表达在一个亚组的rn脊髓神经元中，这些神经元对于控制肢体运动rn的一个协调的运动网络的正常发育非常关键。rn因此，Dmrt3也许在对控制脊椎动物步幅大小rn的脊髓回路进行配置中起一个关键作用。对驯rn化的马来说，DMRT3突变对它们的多样化有rn重大影响，因为若干品种的被改变的步态特征rn显然需要这一突变。本期封面所示为2004年rn在冰岛Hella举行的由纯种冰岛马参加的rn“Landstnot国际马赛”上一匹参赛的马(ArcticrnImages/Corbis)。%Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement1. These networks produce left-right alternation of limbs as well as coordinated activation of flexor and extensor muscles2. Here we show that a premature stop codon in the DMRT3 gene has a major effect on the pattern of locomotion in horses. The mutation is permissive for the ability to perform alternate gaits and has a favourable effect on harness racing performance. Examination of wild-type and Drt3-null mice demonstrates that Dmrt3 is expressed in the dI6 subdivision of spinal cord neurons, takes part in neuronal specification within this subdivision, and is critical for the normal development of a coordinated locomotor network controlling limb movements. Our discovery positions Dmrt3 in a pivotal role for configuring the spinal circuits controlling stride in vertebrates. The DMRT3 mutation has had a major effect on the diversification of the domestic horse, as the altered gait characteristics of a number of breeds apparently require this mutation.

著录项

  • 来源
    《Nature》 |2012年第7413期|p.642-646A2|共6页
  • 作者

    Lisa S. Andersson; Martin Larhammar; Fatima Memic; Hanna Wootz; Doreen Schwochow; Carl-Johan Rubin; KalicharanPatra; Thorvaldur Arnason; Lisbeth Wellbring; GoranHjaelm; Freyja Imsland; JessicaL. Petersen; Molly E. McCue; James R. Mickelson; Gus Cothran; Nadav Ahituv; Lars Roepstorff; Sofia Mikko; Anna Vallstedt; Gabriella Lindgren; Leif Andersson; Klas Kullander;

  • 作者单位

    Department of Animal Breeding and Genetics,Swedish University of Agricultural Sciences,SE-75124 Uppsala,Sweden;

    Department of Neuroscience,Uppsala University,SE-75124 Uppsala,Sweden;

    Department of Neuroscience,Uppsala University,SE-75124 Uppsala,Sweden;

    Department of Neuroscience,Uppsala University,SE-75124 Uppsala,Sweden;

    Department of Animal Breeding and Genetics,Swedish University of Agricultural Sciences,SE-75124 Uppsala,Sweden;

    Department of Medical Biochemistry and Microbiology,Uppsala University,SE-75123 Uppsala,Sweden;

    Department of Neuroscience,Uppsala University,SE-75124 Uppsala,Sweden;

    Faculty of Land and Animal Resources,The Agricultural University of Iceland,IS-311 Borgarnes,Iceland;

    Department of Animal Breeding and Genetics,Swedish University of Agricultural Sciences,SE-75124 Uppsala,Sweden;

    Department of Medical Biochemistry and Microbiology,Uppsala University,SE-75123 Uppsala,Sweden;

    Department of Medical Biochemistry and Microbiology,Uppsala University,SE-75123 Uppsala,Sweden;

    College of Veterinary Medicine,University of Minnesota,St Paul,Minnesota 55108,USA;

    College of Veterinary Medicine,University of Minnesota,St Paul,Minnesota 55108,USA;

    College of Veterinary Medicine,University of Minnesota,St Paul,Minnesota 55108,USA;

    Department of Veterinary Integrative Biosciences,College of Veterinary Medicine and Biomedical Sciences,Texas A&M University,College Station,Texas 77483,USA;

    Department of Bioengineeringand Therapeutic Sciences,University of California San Francisco,San Francisco,California 94143,USA,Institute for Human Genetics,University of California San Francisco,San Francisco,California 94143,USA;

    Unit of Equine Studies,Swedish University of Agricultural Sciences,Uppsala,SE-75007 Sweden;

    Department of Animal Breeding and Genetics,Swedish University of Agricultural Sciences,SE-75124 Uppsala,Sweden;

    Department of Neuroscience,Uppsala University,SE-75124 Uppsala,Sweden;

    Department of Animal Breeding and Genetics,Swedish University of Agricultural Sciences,SE-75124 Uppsala,Sweden;

    Department of Animal Breeding and Genetics,Swedish University of Agricultural Sciences,SE-75124 Uppsala,Sweden,Department of Medical Biochemistry and Microbiology,Uppsala University,SE-75123 Uppsala,Sweden;

    Department of Neuroscience,Uppsala University,SE-75124 Uppsala,Sweden;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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