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研究発表を行った学会；
・第４０回日本発生生物学会・第５９回日本細胞生物学会　合同大会、2007年 5月28~30日(福岡)

タイトル；The regulation of Steroidogenic acute regulatory protein (StAR) gene expression by Dlx5 and Dlx6.
発表者；　西田　尚代　氏
　　　（熊本大学　生命資源研究・支援センター　技術開発分野）
Abstract；
Dlx genes, the vertebrate homolog of Drosophila Distal-less (Dll), play critical roles in the regulation of distal appendage formation. Among the Dlx family of homeodomain transcription factors, Dlx5 and Dlx6 are reported to be involved in the development of subcortical forebrain, branchial arches and limb. Mutations of Dlx5 and Dlx6 genes lead to the human genetic disorder, Split Hand/Foot Malformation 1 (SHFM1), which is occasionally associated with urogenital defects such as micropenis, hypospadias and small testis. Such symptoms are caused by testis abnormalities, but the function of Dlx5 and Dlx6 during testis development is not understood.
In this study, we show that Dlx5 and Dlx6 are expressed in the interstitial region of mouse testis, including Leydig cells that produce testosterone. We found that Dlx5 can regulate the expression of steroidogenic acute regulatory protein (StAR). StAR is essential for adrenal and gonadal steroidogenesis, stimulating the translocation of cholesterol to the inner mitochondrial membrane where the first step of steroidogenesis occurs. Overexpression of Dlx5 induced the activation of StAR gene promoter in a Leydig cell line mLTC-1, whereas the amount of StAR mRNA was decreased in testis of Dlx5, 6 double-knockout (DKO) mice. Importantly, Dlx5, 6 DKO mice showed masculinization phenotypes with decreased testosterone level and anogenital-distance (AGD). These results suggest that Dlx5 and Dlx6 can contribute steroidogenesis through the regulation of StAR gene during the testis development.