Two Labrador dogs called Gene and Geny have been born in South Korea after CRISPR gene editing was used to correct a mutation linked to a common hip disorder. It is the first time that gene editing has been used to attempt to prevent a genetic disorder in dogs, but it won鈥檛 be clear how successful it has been until the dogs are older.
鈥淭he study was performed to develop a procedure for getting rid of harmful mutations from pets,鈥� says team member Okjae Koo at biotech company ToolGen. 鈥淲e believe that Gene and Geny will prove that the correction of harmful mutations by genome editing can cure the diseases of both pets and humans.鈥�
Many pets, especially inbred pedigree ones, have high levels of disease-causing mutations, which breeders sometimes deliberately select for. One common unwanted condition in dogs is hip dysplasia, caused by the hip joint failing to form properly, resulting in pain and difficulty moving as the joint wears out earlier than normal.
Advertisement
Hip dysplasia is hereditary, but factors such as exercise and obesity help determine at what age dogs are affected and how severely. The condition is particularly common in Labradors, golden retrievers, German shepherds and Newfoundlands.
The team, led by Min Kyu Kim at Chungnam National University in South Korea, has previously identified a number of mutations associated with hip dysplasia in dogs. To try to create dogs that are free of the condition, the researchers first took skin cells from the ear of a Labrador with hip dysplasia.
Next, they used a variant of CRISPR gene editing called prime editing to correct one mutation linked to hip dysplasia in the skin cells. The corrected cells were then fused with eggs whose DNA had been removed, to create cloned embryos that were implanted in a surrogate mother.
Gene and Geny are therefore clones of the dog from which the skin cells were taken, but with the mutation corrected. However, it might prove necessary to correct several mutations, not just one, to ensure dogs don鈥檛 develop hip dysplasia, the team warns.
The standard form of CRISPR can induce unwanted mutations along with the intended change, but prime editing is more precise. The team didn鈥檛 find any unwanted mutations in Gene and Geny.
But because of the method used to select corrected cells, the dogs do have some added genes, including one for the fluorescent green protein GFP, meaning they glow green under UV light. 鈥淲e will avoid DNA integration in further studies,鈥� says Koo.
In some countries, there are screening programmes intended to reduce the incidence of hip dysplasia in dogs. In the UK, this involves taking an X-ray of a dog鈥檚 hip after it is at least a year old. The dog is then given . Breeders can avoid breeding dogs with high scores.
鈥淗ip dysplasia can have serious effects on the health, welfare and behaviour of dogs,鈥� says Justine Shotton, president of , 鈥渨hich is why BVA along with The Kennel Club has been running an effective screening scheme since 1965 which is reducing the incidences and severity of the condition in prospective litters.
鈥淕ene editing may offer an alternative to tackling the issue, but this experimental approach still comes with a lot of unknowns, particularly around its unintended consequences, but also the longer-term impacts of intended changes. Animal health and welfare must be a priority, which is why we鈥檙e calling for robust monitoring and reporting.鈥�
The BVA is also calling for the establishment of a regulatory body responsible for reviewing evidence and advising on ethical issues around current and future genetic technologies in animals, says Shotton.
Hip dysplasia affects some people, too. So getting a better understanding of the causes in dogs via gene editing might one day help prevent or treat the disorder in people, the team says.
Scientific Reports
