These Mutant Rabbits Walk on Two Legs, and Geneticists Now Know Why

An entire lineage of French rabbits has been doing handstands for nearly a century. The acrobatic bunnies are not so much performing a stunt as they are a product of stunted genetics, according to a paper published this week in PLOS Genetics.

First discovered in a domesticated rabbit living in a Parisian suburb in 1935, the recessive trait is the product of a genetic mutation that could have been hidden in the animals’ genetic code for generations, only to surface then. It’s not a superpower. The rabbit variety—the “sauteur d’Alfort,” or “the Alfort jumper”—is also more likely to develop cataracts and become blind.

“The strain has been kept since then to study ocular malformations and pathological locomotion,” said co-author Miguel Carneiro, a geneticist at the University of Porto in Portugal, in an email. “Rabbits carrying this mutation would not be able to survive long in the wild due to its deleterious effects.”

The rabbits walk on all fours when moving slowly, but in a rush, turn to the handstand method. Now, a team of geneticists have identified the root of all those problems in the breed’s DNA.

To figure out the origins of the animal’s abnormalities, the team of geneticists and developmental biologists bred the Alfort jumper with rabbits that hop normally and sequenced the DNA of their descendants. They found the rabbits that ended up bipedal had a mutation on the first chromosome; specifically, a warped gene called RORB, which expresses a protein of the same name.

“With modern technology, it’s straightforward to go from a simple recessive disorder to finding the genes,” said co-author Leif Andersson, a geneticist at Uppsala University in Sweden, in a video call. “The expectation was there was something wrong with the spinal cord, because they don’t coordinate their forelegs and the hind legs.”

Among the Alfort jumping rabbits (perhaps a misnomer, given the bunnies have no hops), this was proven true. The RORB protein is a transcription factor, meaning it has a hand in a number of genes, which all end up being expressed in traits. The proteins are ordinarily produced in inhibitory interneurons that cease communications moving through the body. (Imagine an operator refusing to service your calls.) In the weird-walking rabbits, the interneurons either were less present or completely absent, and, in the latter case, the rabbits would overflex their hind legs, rendering them incapable of hopping.

“What’s happening when you’re moving is that you have these neurons firing all the time, and they coordinate muscle contractions and receive feedback on the balance of the different limbs,” Andersson said. “This coordination of muscle contraction is not correct in these rabbits.”

You can think, the rabbits’ handstand is not itself the mutation, but a workaround to an otherwise debilitating inhibition of the animal’s iconic means of locomotion. Andersson said the two-footed locomotion caused the animals no pain of which he was aware.

It’s not the only animal to experience gait disruption due to genetic mutations. Similar behavior was seen in mice with a RORB mutation, and previous work of Andersson’s found that a mutation in the gene DMRT3 disrupts the gait of mice and horses. (Interestingly, it is that mutation at work when you look at the different gait patterns of certain horse breeds, from Tennessee Walkers to Louisiana Fox Trotters.)

Thanks to genetic science, these mysteries can be decrypted on microscopic scales and could aid in better understanding the communication centers of our own (human) spinal cords, for medical research going forward.