A six-legged mouse was created by scientists at the expense of its external genitalia. This specimen provides insights into animal biology and our evolution. The feat, made possible by genetic engineering, could also benefit human medicine, especially for amputated individuals or people born with shortened or no limbs. The findings of this breakthrough experiment were based on a March 2024 study led by researchers from Portugal.

The recent research paper is part of the latest progress in the field of genetics and animal development, particularly when it comes to the modification of body parts. It may seem that the rodent is a product of an experiment gone wrong. However, it gives scientists a new perspective when it comes to unanswered mysteries in evolutionary biology, mainly the formation and development of limbs and hindlimbs.

Six-Legged Mouse Embryo


(Photo : Photo by Ricky Kharawala on Unsplash)

In the paper published in the journal Nature Communications on March 20, a research team from the Gulbenkian Science Institute in Oeiras, Portugal, created a six-legged mouse embryo. The specimen had an extra pair of hindlimbs (the back limbs of an animal) that developed in place of its external genitalia. This is made possible after the researchers inactivated the gene, called Tgfbr1, resulting in the generation of an extra pair of hindlimbs.

The mouse's genitalia is affected although the target of the genetic experiment is the hindlimbs since Tgfbr1 controls key regulatory factors between the two body parts. The discovery seemingly contradicts the long-held notion that the hindlimb and external genital of present-day tetrapods derived from a common ancestor that evolved to develop a wide diversity of body structures that are genetically independent from each other.

Tetrapods pertain to four-legged vertebrate animals, with major groups such as mammals, reptiles, and amphibians. According to the University of California Museum of Paleontology, tetrapods include all terrestrial or land-living vertebrates such as frogs, hawks, lions, and turtles. In relation to the Portugal-led study, researchers were able to identify the said gene, of a certain tetrapod mammal, responsible for affecting both the hindlimb and genitalia.

Also Read: Virgin Births; Fatherless Mice Created in Lab in a Successful Case of Asexual Reproduction

Evolutionary Biology

While it is still unclear if the ground-breaking results of the study applies to humans, it could still pave the way for further research into limb growth for other tetrapod animals. In the field of evolutionary biology, experts say that any land-dwelling tetrapod was once related to a fish that started to crawl on land over 360 million years ago, according to a 2010 Nature study.

In previous research, biologists have pointed out that the evolution of limbs is a result of adaptation for an aquatic animal to survive in shallow waters and eventually travel on land. Although the March 2024 study does not focus on this ancient biological transition, it still gives us a modern approach to evolutionary biology combined with human intervention; specifically, after the creation of the six-limbed mouse.

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