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

Carneiro, Miguel and Vieillard, Jennifer and Andrade, Pedro and Boucher, Samuel and Afonso, Sandra and Blanco-Aguiar, Jose A. and Santos, Nuno and Branco, Joao and Esteves, Pedro J. and Ferrand, Nuno and Kullander, Klas and Andersson, Leif (2021). A loss-of-function mutation in RORB disrupts saltatorial locomotion in rabbits. PLOS GENETICS. 17 , e1009429
[Research article]

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Abstract

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.

Authors/Creators:Carneiro, Miguel and Vieillard, Jennifer and Andrade, Pedro and Boucher, Samuel and Afonso, Sandra and Blanco-Aguiar, Jose A. and Santos, Nuno and Branco, Joao and Esteves, Pedro J. and Ferrand, Nuno and Kullander, Klas and Andersson, Leif
Title:A loss-of-function mutation in RORB disrupts saltatorial locomotion in rabbits
Series Name/Journal:PLOS GENETICS
Year of publishing :2021
Volume:17
Article number:e1009429
Number of Pages:19
Publisher:PUBLIC LIBRARY SCIENCE
ISSN:1553-7404
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 404 Agricultural Biotechnology > Genetics and Breeding
URN:NBN:urn:nbn:se:slu:epsilon-p-111585
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-111585
Additional ID:
Type of IDID
DOI10.1371/journal.pgen.1009429
Web of Science (WoS)000634803500001
ID Code:23338
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Animal Breeding and Genetics
Deposited By: SLUpub Connector
Deposited On:23 Apr 2021 09:03
Metadata Last Modified:23 Apr 2021 09:11

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