On the whole, it is widely accepted that mammals with a Y chromosome are male. However, recent research has produced an exception to the rule. Knocking out a single gene in mice can turn males into females. Researchers breeding a strain of mutant mice lacking a stress-response molecule, namely Gadd45g, wondered why litters produced mainly female pups. Upon closer inspection, they discovered that many of the offspring were in fact genetically male, although they lacked male gonads (shown top left), so looked like females (top right). The researchers discovered that Gadd45g is normally expressed in the same regions of the embryo as Sry, a gene on the Y chromosome known to direct the development of male gonads in the embryo. Evidently without Gadd45g, Sry can’t trigger male gonad development, and female genitalia result. The work uncovers an important piece to the jigsaw of molecular sex determination.
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