title: 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.
authors.affiliation: Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, SE-75124 Uppsala, Sweden.
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Andersson
authors.forename: Martin
authors.initials: M
authors.lastname: Larhammar
authors.forename: Fatima
authors.initials: F
authors.lastname: Memic
authors.forename: Hanna
authors.initials: H
authors.lastname: Wootz
authors.forename: Doreen
authors.initials: D
authors.lastname: Schwochow
authors.forename: Carl-Johan
authors.initials: CJ
authors.lastname: Rubin
authors.forename: Kalicharan
authors.initials: K
authors.lastname: Patra
authors.forename: Thorvaldur
authors.initials: T
authors.lastname: Arnason
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Wellbring
authors.forename: Göran
authors.initials: G
authors.lastname: Hjälm
authors.forename: Freyja
authors.initials: F
authors.lastname: Imsland
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Petersen
authors.forename: Molly E
authors.initials: ME
authors.lastname: McCue
authors.forename: James R
authors.initials: JR
authors.lastname: Mickelson
authors.forename: Gus
authors.initials: G
authors.lastname: Cothran
authors.forename: Nadav
authors.initials: N
authors.lastname: Ahituv
authors.forename: Lars
authors.initials: L
authors.lastname: Roepstorff
authors.forename: Sofia
authors.initials: S
authors.lastname: Mikko
authors.forename: Anna
authors.initials: A
authors.lastname: Vallstedt
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lindgren
authors.forename: Leif
authors.initials: L
authors.lastname: Andersson
authors.forename: Klas
authors.initials: K
authors.lastname: Kullander
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018389:Codon, Nonsense / Q000235:genetics; D005684:Gait / Q000235:genetics* / Q000502:physiology; D020869:Gene Expression Profiling; D005787:Gene Frequency; D006736:Horses / Q000145:classification / Q000235:genetics* / Q000502:physiology*; D007055:Iceland; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009434:Neural Pathways / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D018389:Codon, Nonsense; C473014:Dmrt3 protein, mouse; D014157:Transcription Factors