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Brain gene makes a female develop as a male

2010-12-23
(Press-News.org) Australian scientists have discovered that changes to a gene involved in brain development can lead to testis formation and male genitalia in an otherwise female embryo.

Lead Melbourne researcher Professor Andrew Sinclair, of the Murdoch Childrens Research Institute and the University of Melbourne, said the breakthrough would improve diagnosis and clinical management of patients with disorders of sex development (DSD). These conditions occur when the testes or ovaries do not develop properly in the embryo, causing genital abnormalities in one in 4500 babies.

The gene, called SOX3, sits on the X chromosome and is normally involved in the development of the central nervous system and the brain's pituitary gland. But, scientists found that mutations affecting the SOX3 gene caused it to be abnormally turned on in the embryonic gonad, leading to testis development in human DSD patients and mice.

In males, testis development is regulated by an almost identical gene on the Y chromosome known as SRY. Females have two X chromosomes and therefore do not have an SRY gene.

"We were puzzled by how female embryos could develop testes without the SRY gene," Professor Sinclair said.

"Surprisingly, we found that the SOX3 gene could substitute for the SRY gene in XX female embryos, resulting in the development of testes, male genitalia and a masculine appearance in these patients."

Professor Sinclair said the discovery could explain one in five undiagnosed XX DSD cases, which would help provide a diagnosis and guide clinical management of patients in the future.

The discovery also gives scientists new insight into the evolution of the SRY gene, which is thought to have evolved from the SOX3 gene. It is believed that changes to the SOX3 gene such as those seen in these DSD patients must have occurred millions of years ago, causing the SOX3 gene to be turned on in the gonad and initiate testis development. This mutated SOX3 gene evolved into the Y-linked testis determining gene, SRY.

INFORMATION:

The study, published today by The Journal of Clinical Investigation, was undertaken in collaboration with the University of Adelaide, Women's and Children's Hospital, Adelaide, Prince Henry's Institute for Medical Research, Melbourne, King Edward Memorial Hospital, Perth, University of California, USA, and the National Institute for Medical Research, UK.

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[Press-News.org] Brain gene makes a female develop as a male