Tissue-specific expression of the human CYP19 (aromatase) gene in ovary and adipose tissue of transgenic mice

• Published in: Journal of steroid biochemistry and molecular biology 2001-12, Vol.79 (1), p.193-201
• Main Authors: Hinshelwood, Margaret M, Mendelson, Carole R
• Format: Article
• Language: English
• Subjects: 5' Untranslated Regions; Adipose Tissue - enzymology; Animals; Aromatase; Aromatase - genetics; Artificial Gene Fusion; Biological and medical sciences; Exons; Female; Gene Expression; Human Growth Hormone - genetics; Humans; In Situ Hybridization; Mice; Mice, Inbred ICR; Mice, Transgenic; Ovary - enzymology; Regulation of transcription; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tissue Distribution; Tissue-specific expression
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/S0960-0760(01)00157-1

In humans, the CYP19 (aromatase P450) gene is expressed in a number of tissues, including gonads, placenta, adipose tissue, skin and brain. The 5′-untranslated regions (UTR) of CYP19 mRNA transcripts in these tissues are encoded by different tissue-specific first exons, which are alternatively spliced onto a common site just upstream of the start of translation in exon II. In ovary, the 5′-UTR of CYP19 transcripts is encoded by exon IIa, which lies just upstream of exon II, while in adipose, the 5′-UTR of CYP19 transcripts is encoded by exon I.4, which lies >20 kb upstream of exon II. To map genomic sequences required for ovary- and adipose-specific CYP19 expression, fusion genes containing 2700, 278 and 43 bp of DNA flanking the 5′-end of ovary-specific exon IIa, or 348 bp of 5′- flanking DNA and 170 bp of adipose-specific exon I.4 were linked to the human growth hormone ( hGH) gene, as reporter, and introduced into transgenic mice. We observed that CYP19(IIa):hGH fusion genes containing as little as 278 bp of exon IIa 5′-flanking sequence were expressed at high levels in an ovary-specific manner in transgenic mice, while the CYP19(IIa) −43:hGH fusion gene was not expressed in any tissue. These results suggest that sequences between −43 and −278 bp upstream of exon IIa mediate ovary-specific CYP19 gene expression. In mice carrying the CYP19(I.4) −348:hGH fusion gene, transgene expression was detected in skin and in mammary adipose, but not in any of the other tissues examined. These results indicate that genomic elements within −348 and +170 bp of adipose-specific exon I.4 mediate adipose- and skin-specific CYP19 gene expression. Studies are in progress using transgenic mice to further define the response elements that mediate ovary and adipose-specific hCYP19 gene expression.