Androgen Regulated Development of the Xenopus Larynx

雄激素调节爪蟾喉的发育

• 批准号: 6937866
• 负责人: Brian Thomas Nasipak
• 金额: $ 4.41万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6937866
• 关键词: X ray; Xenopus; androgen receptor; androgens; antineoplastics; cell transplantation; cycloheximide; developmental genetics; dihydrotestosterone; gender difference; gene expression; genetically modified animals; green fluorescent proteins; hormone regulation /control mechanism; larynx; messenger RNA; metamorphosis; myoblasts; myogenesis; predoctoral investigator; tissue /cell culture

DESCRIPTION (provided by applicant): The laryngeal muscle of the anuran Xenopus laevis undergoes a complete switch from a mix of fast and slow twitch muscle fibers to all fast twitch fibers in response to androgen treatment. The proposed experiments will investigate the role of myogenic stem cells (myoblasts) in this androgen response. Mitotic cells, including myoblasts, are first depleted from larynges by the use of anti-neoplastic drugs and radiation. Myoblasts will then be isolated from larynges of animals expressing green fluorescent protein and transplanted back into irradiated larynges in order to determine their ability to rescue the response to androgen. Further experiments will determine whether myoblasts are the target of androgen by rendering larynges androgen insensitive by means of a dominant negative androgen receptor (dnAR). Myoblasts from wild-type larynges will then be transplanted into those expressing the dnAR in order to determine their ability to rescue the androgen response. The final aim of the application is to determine the androgen responsive target genes responsible for fiber type switching.

描述(由申请人提供)：非洲爪哇的喉部肌肉在雄激素治疗下经历了从快和慢抽动肌纤维的混合到全部快抽动肌纤维的完全转换。拟议的实验将研究肌源性干细胞(成肌细胞)在这种雄激素反应中的作用。有丝分裂细胞，包括成肌细胞，首先通过使用抗肿瘤药物和辐射从喉中耗尽。然后，将从表达绿色荧光蛋白的动物的喉部分离成肌细胞，并将其移植回受辐射的喉部，以确定它们拯救雄激素反应的能力。进一步的实验将通过显性的负雄激素受体(DNAR)使喉雄激素不敏感来确定成肌细胞是否是雄激素的靶标。然后，来自野生型喉的成肌细胞将被移植到表达DNAR的成肌细胞中，以确定它们拯救雄激素反应的能力。这项应用的最终目标是确定负责纤维类型转换的雄激素反应靶基因。