TESTIS DEVELOPMENT IN XY SEX REVERSAL

描述(改编自《调查者摘要》)：发展 男性性腺依赖于性别决定基因的功能 (SRY)存在于Y染色体上。人们普遍认为，斯里 启动一连串的基因相互作用，将未分化的 性腺变成了睾丸。在某些情况下，睾丸分化甚至在 Y染色体的存在。这种“性反转”存在于人类身上 导致XY雌性不孕症高发的人群 性母细胞瘤和/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 研究还将深入了解性腺的作用机制。 发展。 这项建议涉及Sry在男性性腺发育中的作用 采用性反转XYDO小鼠模型。在XYDOM性别反转中，Y 家蝇染色体诱发睾丸的能力各不相同。 菌株C57BL/6.阐明XYDOM性逆转的分子基础 P.I.提出了以下具体目标的实验：1. XYDOM性别人群睾丸分化过程中Sry表达的定量研究 反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.确定是否处于次优状态 SRY基因的翻译有助于XYDOM的性别逆转。3.描述 癌基因Kit加剧XYDOM性别的分子机制 反转。4.刻画苗勒式抑制的相互关系 物质和XYDOM的性逆转。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.