性反转是一类因性别分化异常所导致的生殖系统异常发育疾病。46，XY男性性反转因其发生率高，发病机制尚不完全明确而备受关注。本课题组前期对同一家族两名男性性反转患者基因组测序发现，其SOX17基因3’-UTR存在相同单核苷酸突变（SNP）。结合文献，我们推测该突变可能通过干扰SOX17 mRNA稳定性，上调Wnt4/β-catenin通路活性导致性反转的发生。为此，本研究拟利用临床样本及SOX17基因敲除/突变小鼠模型,联合RT-PCR，Western-Blot，ChIP，荧光素酶活性检测及mRNA降解实验等揭示SOX17在男性性腺发育中的作用，并证实SOX17 3’-UTR SNP通过干扰mRNA稳定性减少其蛋白表达，降低对β-catenin的转录抑制，上调Wnt4/β-catenin通路活性导致男性性反转的发生。本研究旨在进一步揭示男性性反转发生的原因及机制，以期为临床干预提供理论支撑。

Sex reversal is a kind of abnormal developmental disease of reproductive system caused by abnormal sex differentiation.46, XY male sex reversal has attracted much attention due to its high incidence and unclear pathogenesis. In our previous study, we sequenced the genomes of two male patients with sex reversal in the same family and found that the same single nucleotide mutation (SNP) existed in the 3 '-UTR of SOX17 gene. Combined with the literature, we speculated that this mutation may lead to the occurrence of sex reversal by interfering with the stability of SOX17 mRNA and up-regulating the activity of Wnt4/ β-catenin pathway. Therefore, this study intends to use the clinical samples and SOX17 knockout/mutant mice model of joint RT-PCR, Western Blot, ChIP, Luciferase activity detection and mRNA degradation experiments reveal SOX17 role in male gonad development, and confirmed that SOX17 3 '- UTR SNP by interfering with mRNA stability to reduce its protein expression, lowering the β-catenin transcription inhibition, increase Wnt4 /β-catenin pathway activity lead to the occurrence of male sex reversal. The purpose of this study is to further reveal the causes and mechanisms of male sex reversal in order to provide theoretical support for clinical intervention.