Somatic support cell function in gonad development

描述（由申请人提供）：异常性别决定导致性别逆转的发生率约为1 / 15000；最常见的病例为XY型女性（Dewing et al., 2002）。事实上，大多数人类性别逆转病例仍然无法解释，这需要更好地理解所有涉及性腺性别决定和分化的基因。本实验旨在验证XX和XY胚胎性腺体细胞支持细胞（somatic support cells, ssc）表达的基因在哺乳动物性腺性别决定和分化中发挥重要作用的假设。本研究的目的是：(1)利用微阵列分析技术鉴定XY和XX胚胎小鼠性腺ssc中差异表达的基因。将通过流式细胞术从含有EGFP报告结构的转基因小鼠的未分化和分化胚胎性腺中分离出SSCs。(2)确定与B6 FOG2 XY性别逆转相关的常染色体修饰位点。FOG2是一种在ssc中表达的核蛋白。Fog2空等位基因（Fog2-）在C57BL/6J （B6）小鼠中引起卵巢发育，而在DBA/2J (D2) XY小鼠中不起作用。全基因组连锁分析将使用单核苷酸多态性（SNP）标记进行。参与B6 FOG2 XY性别逆转的染色体区域将与先前发现的参与其他XY性别逆转模型的B6常染色体位点进行比较。该实验将鉴定在性腺ssc中表达的基因，这些基因在性腺XY性逆转中起作用。

DESCRIPTION (provided by applicant): Abnormal sex determination leading to sex reversal occurs in approximately 1 in 15,000 births; the most frequently observed cases involve XY females (Dewing et al., 2002). The fact that the majority of human sex reversal cases remain unexplained requires a better understanding of all the genes involved in gonadal sex determination and differentiation. The proposed experiments are designed to test the hypothesis that genes expressed in somatic support cells (SSCs) of XX and XY embryonic gonads play an important role in mammalian gonadal sex determination and differentiation. Aims of this proposal are: (1) Identify genes differentially expressed in SSCs of XY and XX embryonic mouse gonads using microarray analysis. SSCs will be isolated by flow cytometry from undifferentiated and differentiated embryonic gonads of transgenic mice containing an EGFP reporter construct expressed specifically in the gonadal SSCs. (2) Identify the autosomal modifier loci involved in B6 FOG2 XY sex reversal. FOG2 is a nuclear protein expressed in SSCs. A Fog2 null allele (Fog2-) causes ovarian development in C57BL/6J (B6) but not in DBA/2J (D2) XY mice. Genome-wide linkage analysis will be performed using single nucleotide polymorphic (SNP) markers. Chromosomal regions involved in B6 FOG2 XY sex reversal will be compared to previously identified B6 autosomal loci involved in other XY sex reversal models. The proposed experiments will identify genes expressed in gonadal SSCs that play a role in gonadal XY sex reversal.