FOLLICULOGENESIS: IMMORTALIZED GRANULOSA CELL LINES

卵泡发生：永生化颗粒细胞系

• 批准号: 6138808
• 负责人: DAVID W SCHOMBERG
• 金额: $ 7.7万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6138808
• 关键词: BCL2 gene /protein; apoptosis; biotechnology; cell cycle; cell line; cell transformation; chemical carcinogen; chemical carcinogenesis; diethylstilbestrol; estrogen receptors; follicle stimulating hormone; gene targeting; genetically modified animals; granulosa cell; histopathology; hormone receptor; immunocytochemistry; laboratory mouse; northern blottings; ovary neoplasms; receptor expression; southern blotting; technology /technique development

DESCRIPTION (Adapted from Applicant's Description): The major objective of this project is to utilize transgenic technology to develop immortalized granulosa cell (GC) lines which will maintain functional Follicle-stimulating hormone receptor (FSHR). In pilot studies, the investigators prepared a FSHR gene-promoter-SV40-T-antigen cDNA construct which targeted T-antigen (Tag) mRNA expression specifically to the gonads of the F1 mice. Their rationale is based upon the transgenic approach of Windle et al (Mol Endo 4:597,1990) in which LH alpha-subunit gene promoter-SV40-T-antigen cDNA constructs produced anterior pituitary tumors, from which immortalized LH-secreting cell lines were derived. They propose to develop FSHR-expressing GC lines in the same manner, but have extended the approach to the F2 generation because GC tumors did not develop in their hemizygous F1 offspring. The objectives will be to: 1) accelerate the development of tumors in the homozygous mice by neonatal DES treatment; and 2) develop and characterize GC lines from the Tag-induced and/or DES-Tag-induced ovarian tumors in terms of FSHR expression and responsiveness. FSHR- expressing cells will provide a powerful tool to study folliculogenesis at the molecular level. Their availability may allow the investigators in an expanded application to determine the mechanism(s) by which the pathways of mitosis and apoptosis in GC are uniquely regulated by FSH. They may also provide a critically important resource for molecular biological studies of ovarian cellular function.

描述（改编自申请人描述）：主要目标