Possibly relevant human trait(s) and/or gene(s) (MIM number): 601972 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2021

Species-specific name: disrupted saltatorial locomotion, sauteur phenotype

Species-specific symbol: s^am

Species-specific description: Carneiro et al. (2021): "Saltatorial locomotion is a type of hopping gait that in mammals can be found in rabbits, hares, kangaroos, and some species of rodents. ... 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. ... Additional anatomical problems have also been described in sauteur rabbits, they are born blind because of retinal dysplasia and start developing cataracts after their first year of life [Theret, 1961; Boucher et al., 1996]."

Inheritance: Carneiro et al. (2021): "The sauteur phenotype, including abnormal gait and ocular lesions, has a simple genetic basis controlled by a single autosomal recessive allele (s^am) [Letard, 1935; Boucher et al., 1996]."

Mapping: Carneiro et al. (2021) employed a bulked segregant analysis to map the causal locus for the sauteur phenotype to a 5.4 Mb region on chromosome 1.

Molecular basis: Using the whole-genome sequencing data generated for the bulked segregant analysis, Carneiro et al. (2021) searched the 5.4 Mb candidate region for potential causal variants and identified a splice site mutation in RORB as likely causal variant. "This variant corresponds to a change from GT to AT in the 5’ donor site of intron 9 (chr1: 61,103,503bp)" (Carneiro et al., 2021). RORB cDNA analysis identified a high proportion of aberrant RORB transcripts in sauteur rabbits (Carneiro et al., 2021).

Pathology: Carneiro et al., 2021: "immunohistochemistry (IHC) was performed on the spinal cord of newborn rabbits from our experimental cross. ... In rabbits homozygous for the wild-type allele, RORB is localized in the nucleus of a population of dorsal horn neurons. ... In the spinal cord from rabbits heterozygous for the sauteur allele (+/s^am), the number of neurons expressing RORB was approximately 25% lower than in the wild-type animals ... . In contrast, in rabbits homozygous for the sauteur allele (s^am/ s^am), the expression of RORB was undetectable by IHC."

Breed: Sauteur d'Alfort.

Associated gene: