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Sry requires a CAG repeat domain for male sex determination in Mus musculus.

Bowles J., Cooper L., Berkman J., Koopman P.

SRY, the mammalian Y-chromosomal sex-determining gene, encodes a protein characterized by a DNA-binding and -bending domain referred to as the HMG box. Despite the pivotal role of this gene, only the HMG box region has been conserved through evolution, suggesting that SRY function depends solely on the HMG box and therefore acts as an architectural transcription factor. In mice (genus Mus) Sry also includes a large CAG trinucleotide repeat region encoding a carboxy-terminal glutamine-rich domain that acts as a transcriptional trans-activator in vitro. The absence of this or any other potential trans-activating domain in other mammals, however, has raised doubts as to its biological relevance. To test directly whether the glutamine-rich region is required for Sry function in vivo, we created truncation mutations of the Mus musculus musculus Sry gene and tested their ability to induce testis formation in XX embryos using a transgenic mouse assay. Sry constructs that encode proteins lacking the glutamine-rich region were unable to effect male sex determination, in contrast to their wild-type counterparts. We conclude that the glutamine-rich repeat domain of the mouse Sry protein has an essential role in sex determination in vivo, and that Sry may act via a fundamentally different biochemical mechanism in mice compared with other mammals.

Nat. Genet. 22:405-408(1999) [PubMed] [Europe PMC]

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