A painstaking triple-gene-knockout study in mice reported in Nature (Vol. 426, No. 6964, 20 Nov 03; pp. 291-295) reveals new and unexpected roles for the insulin receptor family in male sexual development. It moves researchers a step closer to understanding how the Y chromosome gene Sry drives the development of testes.
Luis F. Parada and his colleagues produced mouse embryos that lacked the function of all three members of the insulin receptor family of genes; these genes regulate various aspects of growth and metabolism. None of the three single-knockout mouse strains had defects in sexual development.
Triple-knockout embryos with one X and one Y chromosome showed complete male-to-female sex reversal very early on in development. Their gonads resembled normal XX ovaries in appearance and in the expression of ovary-specific genes, but lacked the expression of testis marker genes.
It seems that the three insulin receptors act upstream of Sry to control sex determination but are not absolutely required for Sry expression, comments Peter Koopman in an accompanying News and Views article.
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