NORMAL ONSET, BUT PROLONGED EXPRESSION, OF SRY GENE IN THE BG.Y(DOM) SEX-REVERSED MOUSE GONAD

When the Y chromosome of the Mus musculus domesticus mouse (Tirano, It aly) is placed onto the C57BL/6J (B6) background, the XY progeny (B6.Y -DOM) develop only ovaries or ovotestes in fetal life. In the present study, we examined transcription of genes known to be involved in gona dal sex differentiation in the B6.Y-DOM gonad. RNA was isolated from e ach gonad at 10 to 18 days of gestation and subjected to RT-PCR analys is. The results indicate that the onset of Sry, a putative testis-dete rmining gene, transcription was normal, whereas its inactivation was d elayed in all B6.Y-DOM gonads. Transcripts of Mullerian inhibiting sub stance, the earliest biochemical product of fetal Sertoli cells, appea red in the B6.Y-DOM ovotestis slightly later than in the control B6,XY gonad, whereas they were either absent or detected transiently in the B6.Y-DOM ovary. Transcription of 3 beta-hydroxysteroid dehydrogenase and 17 alpha-hydroxylase, essential for testosterone synthesis, were e qually delayed in the B6.Y-DOM ovotestis and completely absent in the B6.Y-DOM ovary. P450 aromatase (P450arom), which converts androgens to estrogens, was transcribed in both control XX and XY gonads at the on set of morphological sexual differentiation. The overall pattern of P4 50arom transcription was delayed by 1 day in both B6.Y-DOM ovotestes a nd ovaries. In conclusion, the testis-determining pathway in the B6.Y- DOM gonad appears to be impaired downstream of Sry transcription, resu lting in persistent Sry transcripts and a delay in onset of other gene s involved in testicular differentiation. (C) 1994 Academic Press, Inc .