Male mice turned into females using DNA previously thought to be ‘junk’
Finding could lead to treatments for sexual development disorders in humans.
Snipping out a small region of DNA previously considered to be ‘junk’ leads to male mice developing ovaries instead of testes, researchers at the Francis Crick Institute have found. The finding could lead to treatments for sexual development disorders in humans, they say.
During their early development, mammals develop ovaries and become female unless they have a certain amount of a protein known as SOX9 in their developing gonads. SOX9 causes these organs to become testes, which subsequently direct the remainder of the embryo to become male.
The team found that snipping out a small piece of DNA called enhancer 13 (Enh13) shut off the production of SOX9 in male mice with XY chromosomes leading to them developing ovaries.
The amount of SOX9 produced is controlled by a gene called Sry, which is located within the DNA that makes up the Y chromosome. This is why males, who have an X chromosome and a Y chromosome, usually develop testes while females, who have two X chromosomes, do not.
Just two per cent of human DNA contains the ‘code’ to produce proteins – the key building blocks of life. The remaining 98 per cent is known as ‘non-coding’ and was once thought to be unnecessary ‘junk’ DNA, but there is increasing evidence that this is not the case.
Experiments leading to sex reversal in mice have been going on for decades. In 1991, a different team of scientists bred Randy, a chromosomally female (XX)
mouse who developed into a male after the team introduced the Sry gene into the developing embryo.
“We’ve come a long way since Randy and now, for the first time, we’ve demonstrated sex reversal after changing a non-coding region of DNA rather than a protein-coding gene,” said Crick Group Leader Professor Robin Lovell-Badge. “We think Enh13 is probably relevant to human disorders of sex development and could potentially be used to help diagnose some of these cases."
Jason is the commissioning editor for BBC Science Focus. He holds an MSc in physics and was named Section Editor of the Year by the British Society of Magazine Editors in 2019. He has been reporting on science and technology for more than a decade. During this time, he's walked the tunnels of the Large Hadron Collider, watched Stephen Hawking deliver his Reith Lecture on Black Holes and reported on everything from simulation universes to dancing cockatoos. He looks after the magazine’s and website’s news sections and makes regular appearances on the Instant Genius Podcast.