Albino lizards make history as the world's first gene-edited reptiles

Scientists have finally succeeded in creating gene-edited reptiles – with albino lizards the size of a human index finger the first to ever be made.  

Geneticists have struggled in using the powerful gene-editing tool CRISPR on reptiles due to the way they reproduce.

But a few alterations to the method allowed them to successfully alter the genes of the lizards.  

They opted to make the animal albino because it is an obvious mutation that does not harm the animal, and secondly, it could help to treat vision problems in humans. 

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Geneticists have struggled in using the powerful gene-editing tool CRISPR on reptiles due to the way they reproduce but researchers at the University of Georgia tweaked the existing CRISPR and had a six – nine per cent success rate 

Researchers at the University of Georgia tweaked the existing CRISPR method for the reptiles. 

It had previously been thought CRISPR would not work because it requires injecting directly into freshly fertilised eggs or single-cell zygotes.

Lizards, however, fertilise inside the body at unpredictable times. 

Moving single-cell embryos from females is also fraught with issues and they are notoriously difficult to manipulate in a lab environment.   

But a new method, described in the journal Cell, slowed the procedure down while lizard eggs – or unfertilised oocytes – develop.

They saw a transparent membrane over their ovaries allowed them to see all of the developing eggs, including which eggs would be ovulated and fertilised next.  

They decided to inject the CRISPR reagents into the unfertilised eggs within the ovaries and see if it would work.  

Study corresponding author Dr Doug Menke, an associate professor at the University of Georgia, said: ‘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.

‘We wanted to explore anole lizards to study the evolution of gene regulation, since they’ve experienced a series of speciation events on Caribbean islands, much like Darwin’s finches of the Galapagos.

‘Because we are injecting unfertilised eggs, we thought that we would only be able to perform gene editing on the alleles inherited from the mother. 

A few alterations to the mammalian CRISPR method allowed them to successfully alter the genes of the lizards. They opted to make the animal albino because it is an obvious mutation that does not harm the animal, and secondly, it could help to treat vision problems in humans (stock)

‘Paternal DNA isn’t in these unfertilised oocytes. We had to wait three months for the lizards to hatch, so it’s a bit like slow-motion gene editing. 

‘But it turns out that when we did this procedure, about half of the mutant lizards that we generated had gene-editing events on the maternal allele and the paternal allele.’

Roughly between six and nine per cent of the eggs created some offspring that were gene-edited.  

Professor Menke acknowledged the shortcomings of the procedure,especially when compared to the juggernaut of mammalian CRISPR. 

He said: ‘Relative to the very established model systems that can have efficiencies up to 80 per cent or higher, six per cent seems low, but no one has been able to do these sorts of manipulations in any reptile before.

‘There’s not a large community of developmental geneticists that are studying reptiles, so we’re hoping to tap into exciting functional biology that has been unexplored.’   

WHAT IS CRISPR-CAS9?

CRISPR-Cas9 is a tool for making precise edits in DNA, discovered in bacteria.

The acronym stands for ‘Clustered Regularly Inter-Spaced Palindromic Repeats’.

The technique involves a DNA cutting enzyme and a small tag which tells the enzyme where to cut.

The CRISPR/Cas9 technique uses tags which identify the location of the mutation, and an enzyme, which acts as tiny scissors, to cut DNA in a precise place, allowing small portions of a gene to be removed

By editing this tag, scientists are able to target the enzyme to specific regions of DNA and make precise cuts, wherever they like.

It has been used to ‘silence’ genes – effectively switching them off.

When cellular machinery repairs the DNA break, it removes a small snip of DNA.

In this way, researchers can precisely turn off specific genes in the genome.

The approach has been used previously to edit the HBB gene responsible for a condition called β-thalassaemia.