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

English version

Autoři: Miguel Carneiro ^aff001; Jennifer Vieillard ^aff003; Pedro Andrade ^aff001; Samuel Boucher ^aff004; Sandra Afonso ^aff001; José A. Blanco-Aguiar ^aff001; Nuno Santos ^aff001; João Branco ^aff002; Pedro J. Esteves ^aff001; Nuno Ferrand ^aff001; Klas Kullander ^aff003; Leif Andersson ^aff006
Působiště autorů: CIBIO/InBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Vairão, Portugal ^aff001; Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Porto, Portugal ^aff002; Department of Neuroscience, Uppsala University, Uppsala, Sweden ^aff003; Labovet Conseil (Réseau Cristal), Les Herbiers Cedex, France ^aff004; Department of Zoology, Faculty of Sciences, University of Johannesburg, Auckland, South Africa ^aff005; Science for Life Laboratory Uppsala, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden ^aff006; Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, United States of America ^aff007; Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden ^aff008
Vyšlo v časopise: A loss-of-function mutation in RORB disrupts saltatorial locomotion in rabbits. PLoS Genet 17(3): e1009429. doi:10.1371/journal.pgen.1009429
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1009429

Souhrn

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.

Klíčová slova:

Biological locomotion – Gene pool – Genomics – Heterozygosity – Interneurons – Neurons – Rabbits – Spinal cord

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