Scientists have turned male mice into females by snipping out strands of their DNA in work that could shed light on sexual development disorders which arise in humans.

The male mice grew ovaries and female genitalia instead of the more conventional male anatomy after researchers removed small chunks of DNA from the animals’ genetic code.

The findings could help explain why people with XY chromosomes who are missing similar strands of DNA can go on to develop female sex organs, the scientists say. Males are typically born with X and Y chromosomes, while females have two Xs.

Researchers at the Francis Crick Institute in London showed that they could reverse the sex of male mice by deleting a chunk of DNA called enhancer 13, or Enh13 for short. Like 98% of the genome, this section of DNA does not carry any genes that are used to make proteins, the crucial building blocks of living organisms.

“For the first time we’ve demonstrated sex reversal after changing a non-coding region of DNA,” said Robin Lovell-Badge, a geneticist who led the research at the Francis Crick Institute. “We think Enh13 is probably relevant to human disorders of sex development and could potentially be used to help diagnose some of these cases.”



At least half of the sexual development disorders seen in humans have unexplained genetic causes, the scientists say. “The analysis of such patients has mostly focused on the parts of genes that encode proteins, ignoring the parts that control the activity of the gene.” Lovell-Badge said.

Mammal embryos are destined to grow ovaries and become females unless the sex organs get enough of a protein called SOX9 early on in the womb. The protein turns the organs into testes which then steer the embryo down the path to maleness. In the earliest stages of development, levels of SOX9 are driven by a gene on the Y chromosome, explaining why males typically develop testes.

Writing in the journal, Science, the researchers show that Enh13 boosts SOX9 levels at precisely the right time to produce testes. When it was snipped out of the genetic code, male mice went on to become females.

“Our study highlights the important role of what some still refer to as ‘junk’ DNA, which makes up 98% of our genome,” said Nitzan Gonen, another geneticist at the Francis Crick Institute, and first author on the study. “If a single enhancer can have this impact on sex determination, other non-coding regions might have similarly drastic effects.”

Lovell-Badge added: “Even if there is no immediate solution, this can help patients come to terms with their condition and it helps clinicians decide on the best way to manage it. However, it is the understanding of how genes are regulated that might ultimately have the greatest benefit. As we learn more we may be able to develop ways to modulate gene activity to solve a wide range of clinical problems and not just those affecting testis or ovary development.”