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Little and large: Giraffe-type gene edited into mice

Researchers have edited mice with the giraffe-type FGRL1 gene, observing exceptional hypertension resistance and higher bone mineral density.

The unique phenotype of giraffes

Giraffes are easily recognisable amongst a crowd due to their exceptionally long necks and legs. This makes them the tallest terrestrial animals. In addition, giraffes played a key role in the different evolutionary theories, including those of Lamarck and Darwin. Experts believe that their unusual anatomy provides various selective advantages. As well as enabling access to inaccessible food resources, their elevated head position provides an excellent vantage point for detecting predators or competitors. 

Nonetheless, their anatomy is also accompanied by several physiological challenges. The most notable example is the fact that their cardiovascular system has to tolerate two-fold higher systemic blood pressure than most other mammals. Consequently, giraffes have to maintain a stable blood supply to the head without damaging their cardiovascular system. Giraffes also have neuromotor delays due to their long neural networks. Additionally, they require enlarged and strengthened ligaments to support their long, heavy necks. As a result, the giraffe represents a unique case for studying co-adaptation or evolution in several different traits.

Giraffe gene confers resistance

In this study, published in Science Advances, researchers sequenced the genome of a subspecies of the Northern giraffe – Rothschild’s giraffe. The team used a combination of short- and long-read sequencing as well as Hi-C contact maps to improve assembly of the giraffe genome.

Moreover, the researchers compared the genome of this subspecies with that of okapi (forest giraffe) and bovid relatives (e.g. cattle and goats). From this, the team identified 414 giraffe genes that had unique substitutions. Among them, the researchers confirmed that a fibroblast growth factor (FGF) receptor gene – FGFRL1 – contained seven amino acid substitutions that were not found in any other ruminant.

Using CRISPR/Cas9 genome-editing, the team introduced these mutations into the FGRL1 gene of mice. Surprisingly, they found that these mice had an unusual response to the compound Ang-II, which typically induces high blood pressure. These mice also did not present with any cardiovascular damage compared to wild-type mice who were treated with Ang-II. Overall, these mice showed exceptional hypertension resistance and higher bone mineral density, both of which associate with giraffe adaptations to high stature.

The team are looking to further explore any relevant changes to the cardiovascular system due to these giraffe-specific mutations. They hope that these findings will provide insights into the study of hypertension in humans.

Image credit: By wirestock – freepik

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CRISPR / Gene Editing / Heart