Lil Bub is no ordinary cat. Despite the fact that she’s nearly eight years old, the petite tabby remains roughly the size of a kitten. She has extra toes on each paw, no teeth and an undersized jaw that makes her tongue perpetually stick out—in other words, she’s the Peter Pan of the cat world, boasting an appearance of eternal youth that has garnered her more than three million Facebook fans to date.
Now, Michael Price reports for Science magazine, a crowdfunded DNA analysis published on the preprint server bioRxiv offers an in-depth exploration of the genetic mutations underlying Lil Bub’s singular look: One, affecting the so-called Sonic Hedgehog gene, is responsible for the internet sensation’s extra toes, while the other, a variation of the TNFRSF11A gene, is associated with a debilitating bone disease known as osteopetrosis.
According to Tech Times’ Diane Samson, the new research marks the first time this type of osteopetrosis—a rare condition that renders bones unusually dense and stunts growth—has been described in cats. Previously, mutations similar to the one seen in Lil Bub’s genome have been linked with the disease in humans and mice.
Crucially, study co-author Leslie Lyons of the University of Missouri in Columbia tells Price, the scientists’ findings suggest that Lil Bub’s tiny stature and high number of toes are unrelated rather than symptoms of the same syndrome.
Lyons adds, “It was like, ‘Wow, that’s kind of weird, [this] cat has two different rare mutations.’”
The study, led by geneticists Darío Lupiáñez of the Max-Delbrück Center for Molecular Medicine in Berlin, Daniel Ibrahim of the Max Planck Institute for Molecular Genetics in Berlin and Orsolya Symmons of the University of Pennsylvania, stems from a crowdfunding campaign launched in 2015. In total, nearly 250 donors contributed $8,225 to the project, fittingly nicknamed “The LilBubome.”
As Gizmodo’s Kiona Smith-Strickland explained at the time of the project’s launch, the scientists set out to study Lil Bub’s genome because they hoped her DNA would yield insights applicable to not only other felines, but an array of mammal species, including humans.
“[In] all of these diseases, the mechanism is shared basically between different mammals,” Symmons told Smith-Strickland. “Lil Bub is basically one piece of a puzzle, but she’s also connected to all these other cases.”
Currently, the authors write in the study, the only known treatment for osteopetrosis in humans is a bone marrow transplant. Although Lil Bub suffers from many of the symptoms exhibited by humans with her condition—as owner Mike Bridavsky tells the Conscious Cat’s Ingrid King, by the time she was a year and a half old, the brittle bone disease had left her almost completely immobile—she has been able to avoid this extreme form of treatment, instead relying on regular sessions of pulsed electromagnetic field therapy to improve her mobility.
Given Lil Bub’s unique status as the only validated case of feline osteopetrosis, it remains uncertain whether the therapy that enables her to run, play and jump could be successfully used to treat other mammal species. As the study’s authors point out, no scientific basis for the treatment method currently exists.
Still, Lyons notes in her interview with Science magazine’s Price, the information yielded by Lil Bub’s genome could have positive implications for researchers’ understanding of osteopetrosis.
Lyons concludes, “Humans have this disease, too, and knowing more about how this mutation functions might help lead to a tailored therapy with precision medicine that affects the gene.”