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Research article - Peer-reviewed, 2021

A loss-of-function mutation in RORB disrupts saltatorial locomotion in rabbits

Carneiro, Miguel; Vieillard, Jennifer; Andrade, Pedro; Boucher, Samuel; Afonso, Sandra; Blanco-Aguiar, Jose A.; Santos, Nuno; Branco, Joao; Esteves, Pedro J.; Ferrand, Nuno; Kullander, Klas; Andersson, Leif


Saltatorial locomotion is a type of hopping gait that in mammals can be found in rabbits, hares, kangaroos, and some species of rodents. The molecular mechanisms that control and fine-tune the formation of this type of gait are unknown. Here, we take advantage of one strain of domesticated rabbits, the sauteur d'Alfort, that exhibits an abnormal locomotion behavior defined by the loss of the typical jumping that characterizes wild-type rabbits. Strikingly, individuals from this strain frequently adopt a bipedal gait using their front legs. Using a combination of experimental crosses and whole genome sequencing, we show that a single locus containing the RAR related orphan receptor B gene (RORB) explains the atypical gait of these rabbits. We found that a splice-site mutation in an evolutionary conserved site of RORB results in several aberrant transcript isoforms incorporating intronic sequence. This mutation leads to a drastic reduction of RORB-positive neurons in the spinal cord, as well as defects in differentiation of populations of spinal cord interneurons. Our results show that RORB function is required for the performance of saltatorial locomotion in rabbits.Author summaryRabbits and hares have a characteristic jumping gait composed of an alternate rhythmical movement of the forelimbs and a synchronous bilateral movement of the hindlimbs. We have now characterized a recessive mutation present in a specific strain of domestic rabbits (sauteur d'Alfort) that disrupts the jumping gait. The mutation causing this defect in locomotion pattern occurs in the gene coding for the transcription factor RORB that is normally expressed in many regions of the nervous system especially in the spinal cord dorsal horn. Our results show that expression of RORB is drastically reduced in the spinal cord of affected rabbits which results in a developmental defect. This study is an advance in our understanding how locomotion is controlled in vertebrates.

Published in

2021, volume: 17, number: 3, article number: e1009429

Authors' information

Carneiro, Miguel
Universidade do Porto
Vieillard, Jennifer
Uppsala University
Andrade, Pedro
Universidade do Porto
Boucher, Samuel
Réseau Cristal
Afonso, Sandra
Universidade do Porto
Blanco-Aguiar, Jose A.
Universidade do Porto
Santos, Nuno
Universidade do Porto
Branco, Joao
Universidade do Porto
Esteves, Pedro J.
Universidade do Porto
Ferrand, Nuno
University of Johannesburg
Kullander, Klas
Uppsala University
Andersson, Leif
Uppsala University
Andersson, Leif
Texas A&M University
Andersson, Leif
Swedish University of Agricultural Sciences, Department of Animal Breeding and Genetics

UKÄ Subject classification

Genetics and Breeding

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