Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice.
Abstract: Locomotion in mammals relies on a central pattern-generating circuitry of spinal interneurons established during development that coordinates limb movement. These networks produce left-right alternation of limbs as well as coordinated activation of flexor and extensor muscles. 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 Dmrt3-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.
Publication Date: 2012-08-31 PubMed ID: 22932389PubMed Central: PMC3523687DOI: 10.1038/nature11399Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
Summary
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This paper explains how mutations in the DMRT3 gene can significantly influence the pattern and alternation of limb movement in horses and affect the function of spinal cord neurons in mice.
Introduction
The central pattern-generating circuitry, composed of spinal interneurons, assures coordinated limb movement and proper locomotion in mammals. The DMRT3 gene has been identified as essential for the function of this neural network. Mutations in this gene can affect a mammal’s mobility, especially evident in horses’ alternate gait patterns and race performance.
Investigation in Horses and Mice
- The research team discovered a premature stop codon in the horses’ DMRT3 gene – indicating a significant mutation. They found that this mutation directly affects the pattern of locomotion.
- This mutation allows horses to perform alternate gaits and give improved performances in harness racing.
- A parallel examination of wild-type and Dmrt3-null mice was conducted to understand the gene’s role across species.
- In mice, Dmrt3 is implicated in the dI6 subdivision of spinal cord neurons. This gene significantly aids in neuron specification within the subdivision.
- The Dmrt3 gene was found vital for the normal development and functioning of a locomotor network controlling the limb movement.
Impact Beyond Basic Understanding
- The findings from this research have broader implications in veterinary science, particularly for domestic horses. The DMRT3 mutation is believed to be necessary for altered gait characteristics – a property that significantly defines various horse breeds.
- This breakthrough discovery not only explains some diversity seen in domestic horses but also broadens our understanding of vertebrate locomotion at a genetic level.
Conclusion
This research identified the DMRT3 gene’s essential role in coordinating the spinal circuits controlling stride in vertebrates. Mutations in this gene significantly influence locomotion, demonstrated in horses’ gait pattern changes and mice’s spinal circuit function aberrations.
Cite This Article
APA
Andersson LS, Larhammar M, Memic F, Wootz H, Schwochow D, Rubin CJ, Patra K, Arnason T, Wellbring L, Hjälm G, Imsland F, Petersen JL, McCue ME, Mickelson JR, Cothran G, Ahituv N, Roepstorff L, Mikko S, Vallstedt A, Lindgren G, Andersson L, Kullander K.
(2012).
Mutations in DMRT3 affect locomotion in horses and spinal circuit function in mice.
Nature, 488(7413), 642-646.
https://doi.org/10.1038/nature11399 Publication
Researcher Affiliations
- Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, SE-75124 Uppsala, Sweden.
MeSH Terms
- Amino Acid Sequence
- Animals
- Codon, Nonsense / genetics
- Gait / genetics
- Gait / physiology
- Gene Expression Profiling
- Gene Frequency
- Horses / classification
- Horses / genetics
- Horses / physiology
- Iceland
- Mice
- Molecular Sequence Data
- Mutation / genetics
- Neural Pathways / physiology
- Psychomotor Performance / physiology
- Spinal Cord / cytology
- Spinal Cord / physiology
- Transcription Factors / deficiency
- Transcription Factors / genetics
- Transcription Factors / metabolism
Grant Funding
- R01 HD059862 / NICHD NIH HHS
- R01HD059862 / NICHD NIH HHS
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