Gubbay, John Ernest; (1992) A molecular genetic analysis of testis determination in the mouse. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The testis determining gene is the Y-linked gene responsible for initiating the developmental pathway leading to testis formation in males. A strategy based upon determining the precise chromosomal location of this locus has been used to clone candidate genes. In this study members of the ZF7 gene family have been analysed in terms of their expression pattern and their functional status in XY female mice known to be defective in the testis determining gene. The failure to detect any molecular abnormality in ZFY genes in these mice, their inappropriate expression pattern and other data show that these genes cannot be involved in testis determination. A second candidate gene known as SRY was subsequently isolated in humans, also by positional cloning. This study describes the cloning of the homologous gene in mouse (Sry) and presents data showing that this is indeed the testis determining gene. Its chromosomal location and putative protein structure are consistent with a role in sex determination. Sry seems to be the only gene affected in XY female mice, indicating that it is normally necessary for testis determination. Models for how the deletion event which gave rise to these XY female mice occurred are considered in the light of the unusual genomic organisation found at the Sry locus. Finally, the finding that a genomic fragment carrying Sry can cause male development in XX mice has proved that Sry is the only gene from the Y chromosome necessary for testis determination.

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