A 278 bp region just upstream of the human CYP19 (aromatase) gene mediatesovary-specific expression in transgenic mice

In humans, the CYP19 gene. which encodes aromatase P450, is expressed in a number of tissues including gonads, adipose, bone, and placenta. The 5'-unt ranslated regions (UTR) of CYP19 mRNA transcripts in these tissues are enco ded by different tissue-specific first exons, which are alternatively splic ed onto a common site just upstream of the start site of translation in exo n II. In ovary, the 5'-UTR of CYP19 transcripts is encoded by exon IIa, whi ch lies just upstream of exon II. To map genomic sequences required for ova ry-specific CYP19 expression, fusion genes containing 2700, 278 and 43 bp o f exon IIa 5'-flanking DNA linked to the human growth hormone, hGH gene, as reporter. were introduced into mice. CYP19(IIa).(2700):hCH and CYP19(II).( 278):hCH transgenes were expressed at high levels in ovaries of transgenic mice, whereas, ovarian expression of CYP19(IIa).(43):hCH was undetectable. In the majority of mice carrying the CYP19(IIa).(2700):hGH and CYP19(IIa).( 278):hCH fusion genes, transgene expression was ovary-specific, indicating that genomic sequences within 278 bp region mediate ovary-specific expressi on. Expression of CYP19(IIa).(2700):hGH and CYP19(IIa).(278):hGH fusion gen es was detected in ovarian granulosa and luteal cells, as well as in lutein ized interstitial cells in mice during the estrous cycle. The most intense hGH immunostaining was observed in corpora lutea. This pattern of transgene expression is similar to that of aromatase in women where both granulosa a nd luteal cells express aromatase during the menstrual cycle. These finding s suggest that transgenic mice provide an excellent model for analyzing gen omic regions that mediate ovary-specific expression of the human CYP19 gene .