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


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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