Gonadal tumorigenesis in transgenic mice bearing the mouse inhibin alpha-subunit promoter/simian virus T-antigen fusion gene: characterization of ovarian tumors and establishment of gonadotropin-responsive granulosa cell lines.
Gonadal tumorigenesis in transgenic mice bearing the mouse inhibin alpha-subunit promoter/simian virus T-antigen fusion gene: characterization of ovarian tumors and establishment of gonadotropin-responsive granulosa cell lines.
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DOI：
10.1210/mend.9.5.7565808
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发表时间：
1995-05
影响因子：
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通讯作者：
K. Kananen;M. Markkula;E. Rainio;J. Su;A. Hsueh;I. Huhtaniemi
中科院分区：
文献类型：
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作者：
K. Kananen;M. Markkula;E. Rainio;J. Su;A. Hsueh;I. Huhtaniemi
为了建立体内性腺肿瘤模型和性腺体细胞永久系，我们生产了表达猿病毒（SV）40 T-抗原（T-ag）的转基因（TG）小鼠，由小鼠抑制素α亚基启动子的6或2.1千碱基片段驱动。迄今为止，共有 44 只 TG 小鼠（其中一只携带较短的转基因）产生了性腺肿瘤。详细研究了表达较长转基因 KK1 和 KK3 的两只创始雌性小鼠以及三个已建立的 TG 小鼠系。 IT6-M 和 IT6-F 小鼠系中表型的外显率为 100%（肿瘤/TG：IT6-M 22/22，IT6-F 14/14）。 T-ag mRNA 在性腺、肾上腺、垂体和大脑中强烈表达。用抗 SV40 大 T 抗体对 KK-1 和 KK-3 卵巢肿瘤细胞进行免疫染色。 KK-1 细胞具有高亲和力 LH 受体 [平衡缔合常数 (Ka = 7.8 x 10(10) 升/摩尔]，并通过升高 cAMP 和黄体酮生成来响应人类 CG。此外，FSH 轻微刺激其 cAMP 和雌二醇生成 (P < 0.01)。这些细胞表达细胞色素 P450arom 和抑制素 α mRNA，但不表达细胞色素总之，KK-1 细胞是表达内源性促性腺激素受体、类固醇生成酶和抑制素 α 的永生化黄体化颗粒细胞。这些细胞将有助于研究颗粒细胞功能的分子方面。本研究表明，本文中描述的抑制素 α 启动子的 6 KB 片段包含指导体内组织特异性表达的元件。性腺中的其他基因。
To establish in vivo gonadal tumor models and permanent lines of gonadal somatic cells we produced transgenic (TG) mice expressing the Simian virus (SV) 40 T-antigens (T-ag), driven by 6 or 2.1 kilobase fragments of the mouse inhibin alpha-subunit promoter. Hitherto, altogether 44 TG mice, one of which carried the shorter transgene, have produced gonadal tumors. Two founder females expressing the longer transgene, KK1 and KK3, and three established TG mouse lines were studied in detail. Penetrance of the phenotype in IT6-M and IT6-F mouse lines was 100% (tumors/TG: IT6-M 22/22, IT6-F 14/14). The T-ag mRNA was strongly expressed in the gonads, adrenal glands, pituitary, and brain. The KK-1 and KK-3 ovarian tumor cells immunostained with anti-SV40 large-T antibody. The KK-1 cells possessed high-affinity LH receptors [equilibrium association constant (Ka = 7.8 x 10(10) liters/mol] and responded to human CG by elevated cAMP and progesterone production. Also FSH slightly stimulated their cAMP and estradiol production (P < 0.01). These cells expressed cytochrome P450arom and inhibin alpha mRNA, but not cytochrome P450c17 alpha. In conclusion, the KK-1 cells are immortalized luteinizing granulosa cells expressing endogenous gonadotropin receptors, steroidogenic enzymes, and inhibin alpha. These cells will be useful in studies on the molecular aspects of granulosa cell function. The present study indicates that the 6-kilobase fragment of the inhibin alpha promoter described in this article contains the elements directing tissue-specific expression in vivo and is useful for targeted expression of other genes in the gonads.