Understanding sex differences in physiology and disease requires the identification of the molecular agents that cause phenotypic sex differences. Two groups of such agents are genes located on the sex chromosomes, and gonadal hormones. The former have coherent linkage to chromosomes that form differently in the two sexes under the influence of genomic forces that are not related to reproductive function, whereas the latter have a direct or indirect relationship to reproduction. Evidence published in the past 5 years supports the identification of several agents of sexual differentiation encoded by the X chromosome in mice, including Kdm5c, Kdm6a, Ogt and Xist. These X chromosome agents have wide pleiotropic effects, potentially influencing sex differences in many different tissues, a characteristic shared with the gonadal hormones. The identification of X chromosome agents of sexual differentiation will facilitate understanding of complex intersecting gene pathways underlying sex differences in disease.

了解生理学和疾病中的性别差异需要识别导致表型性别差异的分子因子。两组此类因子是位于性染色体上的基因和性腺激素。前者与在与生殖功能无关的基因组力的影响下在两种性别中以不同方式形成的染色体具有连贯的连锁，而后者与生殖有直接或间接的关系。过去 5 年发表的证据支持小鼠 X 染色体编码的几种性别分化因子的鉴定，包括Kdm5c 、 Kdm6a 、 Ogt和Xist 。这些 X 染色体制剂具有广泛的多效性作用，可能影响许多不同组织的性别差异，这是与性腺激素共有的特征。鉴定性别分化的 X 染色体因子将有助于理解疾病性别差异背后的复杂交叉基因途径。