Single-DNA-letter tweak triggers male genitalia in female mice

Scientists edited Enh13, a non-coding enhancer that helps turn on SOX9, in female mouse embryos by deleting three nucleotides or inserting one; the result was that XX mice developed small testes and male external genitalia, while retaining some ovarian tissue. For male organs to form, both copies of Enh13 had to be mutated; one mutated copy yielded normal ovaries. The finding suggests that even tiny changes in regulatory DNA can trigger a male-development cascade via a weak SOX9 activation, shedding light on how some human sex-development disorders might arise.