Scientists create albino lizards

AFP . Washington | Update:

This undated handout photo obtained 27 August 2019 courtesy of Doug Menke and the University of Georgia shows an albino lizard. Photo: AFPA team of scientists at the University of Georgia has successfully performed gene-editing on reptiles for the first time, creating a pair of albino lizards the size of a human index finger.

In a paper describing the breakthrough in the journal Cell Press on Tuesday, the researchers said it could help us better understand vision problems in humans with albinism.

The powerful gene-editing technology known as CRISPR has led to big breakthroughs in mice, plants and humans, but getting it to work on reptiles had proved impossible because of key reproductive differences.

"For quite some time we've been wrestling with how to modify reptile genomes and manipulate genes in reptiles, but we've been stuck in the mode of how gene editing is being done in the major model systems" said Doug Menke, co-author of a paper that described the work in Cell Press on Tuesday.

By contrast, gene-editing techniques have been researched extensively on so-called "major model systems" like mice, chicken, and certain species of fish and frogs.

CRISPR gene-editing is usually performed on freshly fertilized eggs or single-cell zygotes, but the technique is difficult to apply to egg-laying animals.

If you try to do it after fertilization, millions of cells will have already grown, and trying to penetrate the leathery, flexible shell at that stage may kill the embryo, Menke told AFP.

The alternative is to perform the technique before fertilization, but injecting the CRISPR reagents too early will mean they're wasted.

That leaves a narrow window for them to be effective, but because sperm gets stored for a long time inside the oviducts of females, it was difficult to guess when fertilization would occur.

Menke and his colleagues noticed that the transparent membrane over the ovary allowed them to see which eggs were going to be fertilized next, and decided to inject the CRISPR reagents into them just before this occurred.

Not only did it work, but, to their surprise, the gene-edits ended up in both the maternal-line and paternal DNA, not just the former as they had predicted.

Human applications
But why did they choose to make the lizards albino?

The first and most obvious reason, said Menke, was to prove their technique had been successful: "If we see an albino lizard, it's really obvious that it's worked."

Second, knocking out the tyrosinase gene, which results in albinism, is not lethal to the animal.

Finally, humans with albinism often have problems with their vision, and researchers can use the index-finger-sized lizards as a model to study how the gene impacts the development of the retina.

"There's a structure in the human eye called the fovea, this kind of pit-like structure really important for high acuity vision, and the major animals used for biomedical research, like mice, don't have it," said Menke.

"So we wanted to develop a new animal model to study fovea defects, and it turns out these lizards need high acuity vision, because when they hunt insects, they have fovea in their eyes."

The team says the technique could also be applied to birds, which have been gene-edited in the past but using more complex processes.

Since bursting onto the scene more than a decade ago, CRISPR (also known by its full name CRISPR-Cas9) has been used for a number of potentially game-changing applications: from reducing the severity of genetic deafness in mice to controversially making human babies immune to HIV.

Menke argued it was essential to expand the scope of animals on which the technique could be applied.

"Each species undoubtedly has things to tell us, if we take the time to develop the methods to perform gene editing," he said.

ia/cs

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