TESTIS DEVELOPMENT IN XY SEX REVERSAL

描述（改编自研究者摘要）： 雄性性腺依赖于性别决定基因座的功能 (Sry)存在于Y染色体上。 人们普遍认为， 启动一系列基因相互作用， 生殖腺进入睾丸 在某些情况下，睾丸分化失败，甚至在 Y染色体的存在。 这种“性逆转”存在于人类 导致不育XY女性发生率高的人群 性腺母细胞瘤和/或恶性生殖细胞肿瘤。 了解 因此，这种表型的发生是一个重要的健康问题。 这些 研究还将提供一个深入了解性腺的机制， 发展 该提案涉及Sry在男性性腺发育中的作用 使用性反转XYDO小鼠模型。 在XYDOM性别逆转中，Y M.在不同的环境中， 菌株C57 B1/6。 阐明XYDOM性逆转的分子基础 私家侦探提出实验沿着以下具体目标：1. XYDOM性别小鼠睾丸分化过程中Sry表达的定量研究 逆转菌株，以确定性逆转是否是由于延迟 Sry的启动和/或次优表达。2. 确定是否为次优 Sry mRNA翻译有助于XYDOM性逆转。 3. 表征 癌基因Kit加剧XYDOM性行为的分子机制 逆转 4. 描述苗勒管抑制的相互关系 物质和XYDOM性逆转。 5. 生成和表征 永生化胎儿性腺细胞系和XYSxr胚胎生殖细胞， 补充XYDOM性逆转研究。

DESCRIPTION (Adapted from the Investigator's Abstract): The development of the male gonad is dependent on the function of the sex determining locus (Sry) present on the Y chromosome. It is generally believed that Sry initiates a cascade of gene interactions that transforms an undifferentiated gonad into a testis. In some instances testis differentiation fails even in the presence of a Y chromosome. This "sex reversal" is present in the human population causing the development of sterile XY females with high incidence of gonadoblastoma and /or malignant germ cell tumors. Understanding the genesis of this phenotype is therefore an important health issue. These studies will also provide an insight into the mechanisms of gonadal development. This proposal addresses the role of Sry in development of the male gonad using the sex reversal XYDO mouse model. In the XYDOM sex reversal, the Y chromosomes of the M. domesticus vary in their ability to induce testes in the strain C57Bl/6. To elucidate the molecular basis of XYDOM sex reversal the P.I. proposes experiments along the following specific aims: 1. Quantify the Sry expression during testis differentiation in XYDOM sex reversed strains to determine if sex reversal results from a delay in initiation and/or suboptimal expression of Sry. 2. Determine if suboptimal Sry mRNA translation contributes to XYDOM sex reversal. 3. Characterize the molecular mechanism by which the oncogene Kit exacerbates XYDOM sex reversal. 4. Characterize the inter-relationship of Mullerian inhibiting substance and XYDOM sex reversal. 5. Generate and characterize immortalized fetal gonadal cell lines and XYSxr embryonic germ cells to complement XYDOM sex reversal studies.