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© Research
Publication : Proceedings of the National Academy of Sciences of the United States of America

A regulatory cascade hypothesis for mammalian sex determination: SRY represses a negative regulator of male development

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 15 Apr 1993

McElreavey K, Vilain E, Abbas N, Herskowitz I, Fellous M

Link to Pubmed [PMID] – 8475082

Proc. Natl. Acad. Sci. U.S.A. 1993 Apr;90(8):3368-72

The mammalian Y chromosome carries the SRY gene, which determines testis formation. Here we review data on individuals who are XX but exhibit male characteristics: some have SRY; others do not. We have analyzed three families containing more than one such individual and show that these individuals lack SRY. Pedigree analysis leads to the hypothesis that they carry recessive mutations (in a gene termed Z) that allow expression of male characteristics. We propose that wild-type Z product is a negative regulator of male sex determination and is functional in wild-type females. In males, SRY product represses or otherwise negatively regulates Z and thereby allows male sex determination. This hypothesis can also explain other types of sex reversal in mammals, in particular, XY females containing SRY. Some of these individuals may have mutations at the Z locus rendering them insensitive to SRY. Recessive mutations (such as the polled mutation of goats) leading to sex reversal are known in a variety of animals and might be used to map and ultimately clone the human Z gene.

http://www.ncbi.nlm.nih.gov/pubmed/8475082