ANALYSIS OF THE ROLE OF AMH AND FRA1 IN THE SRY REGULATORY PATHWAY

Sry is the Y-chromosomal gene responsible for initiating the pathway o f male development in mammals, presumably by regulating downstream tar get genes. As a basis for examining the role played by Sry and other c andidate sex-determining genes, we have used reverse-transcriptase PCR to produce a precise temporal profile of expression of Sry in the dev eloping gonad. Sry expression first occurs at 10.5 days postcoitum (dp c) and is upregulated to reach a maximum level from 11.25 to 12 dpc. E xpression is then steadily downregulated from 12.25 to 13.25 dpc and i s completely extinguished by 13.5 dpc. Two genes implicated in sexual development are Amh, encoding anti-mullerian hormone (AMH), and Fra1, encoding Fos-related antigen-1. Expression profiles of Amh and Sry in fetal gonads indicate a possible role for AMH in the downregulation of Sry expression. We show, however, that the timing of Sry downregulati on is unaffected in Amh-deficient mice, excluding a role for AMH as a negative regulator of Sry. Further, we have examined the possibility t hat SRY may activate Fra1 during testis determination by analysing the expression of Fra1 in mouse fetal gonads. Fra1 is not expressed at an y stage at or around the critical period of sex determination when Sry transcripts are present, thus excluding a role for Fra1 in sex determ ination and differentiation. (C) 1996 Wiley-Liss, Inc.