SCC-Cre轉殖小鼠之建立－
以人類CYP11A1基因啟動子驅動Cre重組酶的表現

吳曙序

doi:10.6342/NTU.2006.01356

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SCC-Cre轉殖小鼠之建立－以人類CYP11A1基因啟動子驅動Cre重組酶的表現

Generation of SCC-Cre transgenic mice expressing Cre recombinase under control of human CYP11A1 promoter

吳曙序 , Masters　　Advisor：胡孟君　　

繁體中文 DOI： 10.6342/NTU.2006.01356

CYP11A1基因；膽固醇側鏈裂解酶Cre-loxP系統；腎上腺；性腺；精原細胞； CYP11A1 ； P450scc ； Cre-loxP ； ROSA26 ； adrenal gland ； testis ； ovary ； spermatogonia

Abstract │ Reference (46) │ Times Cited (1) │ Altmetrics

Abstract 〈TOP〉

Parallel Abstract 〈TOP〉

Steroid hormones including mineralcorticoids, glucocorticoids, and sex hormones are crucial for a wide variety of physiologic functions. All steroids are converted from a common precursor, cholesterol. The first rate-limiting step of steroidogenesis is catalyzed by cytochrome P450scc, cholesterol side-chain cleavage enzyme, encoded by CYP11A1. Steroid hormones are mainly synthesized in adrenals, gonads and placenta and CYP11A1 is highly expressed in these steroidogenic organs. Recent studies have found that steroids can also be de novo synthesized in brain. However, the expression levels of steroidogenic genes including CYP11A1 in brain are much lower than those in adrenal glands. In this study, a 5’-flanking 4.4-kb region of human CYP11A1 gene was used to target Cre recombinase in transgenic mice, with two-copy HS4 elements of chicken β-globin gene to assure Cre expression and protect transgene against chromosome position effect. The transgenic mice were crossed to floxed ROSA26 reporter mice to examine the Cre activity. By X-gal staining assay, the results showed that the 4.4-kb fragment directed transgene expression in adrenal cortex, Leydig cells of testis and follicles, corpora lutea and stroma of ovary in most of lines, as endogenous Cyp11a1 expression patterns observed by in situ hybridization. In addition, Cre activity was also detected in brain tissues in strong expression lines. We further found that Cre was expressed in the spermatogonia of testis in all transgenic lines. The LacZ protein could be identified in spermatogonia by immunohistochemistry. Low amounts of endogenous P450scc protein in spermatogonia was visualized by IHC. It indicated that spermatogonia have the potential capacity for steroid hormones production. In conclusion, we established a SCC-Cre transgenic mouse line to provide a powerful system for studying the gene function in steroidogenic cell lineages.

Reference ( 46 ) 〈TOP〉

Arensburg J, Payne AH, Orly J. 1999. Expression of steroidogenic genes in maternal and extraembryonic cells during early pregnancy in mice. Endocrinology 140:5220-5232.
連結：
Bakke M, Lund J. 1995. Mutually exclusive interactions of two nuclear orphan receptors determine activity of a cyclic adenosine 3',5'-monophosphate-responsive sequence in the bovine CYP17 gene. Mol Endocrinol 9:327-339.
連結：
Bell AC, West AG, Felsenfeld G. 2001. Insulators and boundaries: versatile regulatory elements in the eukaryotic. Science 291:447-450.
連結：
Carreau S, Lambard S, Delalande C, Denis-Galeraud I, Bilinska B, Bourguiba S. 2003. Aromatase expression and role of estrogens in male gonad: a review. Reprod Biol Endocrinol 1:35.
連結：
Chou SJ, Lai KN, Chung B. 1996. Characterization of the upstream sequence of the human CYP11A1 gene for cell type-specific expression. J Biol Chem 271:22125-22129.
連結：

Times Cited (1) 〈TOP〉

江衍楓(2007)。CYP11A1基因於腦內之表現與調控。臺灣大學生理學研究所學位論文。2007。1-57。

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