CIBIO/InBIO, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Vairão, Portugal.
Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Porto, Portugal.
PLoS Genet. 2021 Mar 25;17(3):e1009429. doi: 10.1371/journal.pgen.1009429. eCollection 2021 Mar.
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.
跳跃式运动是一种跳跃步态，在哺乳动物中可以在兔子、野兔、袋鼠和一些啮齿动物中发现。控制和微调这种步态形成的分子机制尚不清楚。在这里，我们利用一种家养兔子的品系，即 sauterd'Alfort，它表现出一种异常的运动行为，其特征是失去了野生型兔子所具有的典型跳跃。引人注目的是，来自这个品系的个体经常使用前腿采用双足步态。通过实验杂交和全基因组测序的组合，我们表明一个包含 RAR 相关孤儿受体 B 基因 (RORB) 的单一基因座解释了这些兔子的非典型步态。我们发现 RORB 中一个进化保守位点的剪接位点突变导致几个包含内含子序列的异常转录本异构体。这种突变导致脊髓中 RORB 阳性神经元的急剧减少，以及脊髓中间神经元群体分化的缺陷。我们的结果表明，RORB 功能对于兔子的跳跃式运动表现是必需的。
