CRISPR used to control which genes are passed down in mice
Humans have been tinkering with evolution for millennia, breeding plants and animals to favor the traits we want, but new research might make the process a bit more direct. Biologists at the University of California San Diego have successfully used the CRISPR gene-editing tool to control genetic inheritance in mice for the first time.
Normally, inheritance of a particular gene averages out to about 50/50. That means that if a parent has two different versions of a particular gene – one on each chromosome – then, statistically, half of their offspring would have one version and the other half the other. But what if you want to single out one version to pass down?
The new study set out to do just that, using the CRISPR-Cas9 system. This powerful tool allows scientists to make precise edits to the genome of plants, animals and even humans, by snipping out a certain sequence of DNA and replacing it with something else. This can be used, for example, to remove genes that may increase the risk of a disease.
In this case, the researchers engineered an active genetic "CopyCat" DNA element, and used CRISPR to copy it from one chromosome to the other. The idea is that this would increase the chances that this gene would be passed down to the next generation of mice in tests. To make it as easy as possible for the scientists to tell whether it had worked or not, they inserted the CopyCat element into the Tyrosinase gene, which controls fur color. If it worked, the baby mouse would have white fur, and if it didn't it would be black.
Sure enough, the technique was found to increase the rate of genetic inheritance of that particular gene. While the ultimate goal would be for 100 percent of the offspring to carry the desired gene, in this study the researchers hit a top of 86 percent in one family of mice.
This marks the first time this kind of active genetics has been conducted in mammals. In recent years a similar process has been used in insects, for example in making malaria-resistant mosquitoes that will pass that trait down through a population.
Interestingly, the team found that the technique only worked in female mice – edited male mice failed to pass down the desired gene any more than usual. The team chalks it up to differences between sexes in the timing of a cell process called meiosis, which essentially shuffles the genes between the chromosomes inherited by each parent.
In future the team plans to tackle this problem, as well as trying to control the inheritance of multiple genes simultaneously, rather than just the one. Eventually, it could be used to breed mice that more accurately represent models of human diseases to aid in finding treatments.
"Our motivation was to develop this as a tool for laboratory researchers to control the inheritance of multiple genes in mice," says Kimberly Cooper, lead researcher on the study. "With further development we think it will be possible to make animal models of complex human genetic diseases, like arthritis and cancer, that are not currently possible."
The research was published in the journal Nature, and the team describes the work in the video below.